subject:(mechanobiology)

University of Cape Town

1. Smith, Rochelle. Cancer Cell Mechanics in Chemoresistance and Chemotherapeutic Drug Exposure.

Degree: MSc, Human Biology, 2019, University of Cape Town

► Cancer remains a problem worldwide as one of the leading causes of morbidity and mortality. Many cancer patients experience recurrence and ultimately death due to… (more)

▼ Cancer remains a problem worldwide as one of the leading causes of morbidity and mortality. Many cancer patients experience recurrence and ultimately death due to treatment failure or the development of chemoresistance. The concept of chemoresistance however is complex, recent studies have highlighted that cellular structure and extra-cellular composition, mechanics and structure play a role in the development of chemoresistance. The mechanical properties of cells impact their architecture, migration patterns, intracellular trafficking and many other cellular functions. Studies have also revealed that cellular mechanical properties are modified during cancer progression. We investigated these mechanical properties and changes to them by using a malignant melanoma cell line (WM1158) and a chemoresistant malignant melanoma cell line (SK-MEL29). Malignant melanoma was the cell line of choice as it is one of the most prominent types of cancer known to develop chemoresistance. The aim of this study was to identify the effects of chemotherapeutic drug exposure on the mechanical properties and cytoskeletal composition of drug sensitive and drug resistant malignant melanoma cells. To achieve this, a combination of Multiple particle tracking microrheology (MPTM), quantitative RT-PCR and Western blotting techniques were utilised to demonstrate changes in cytoskeletal elements that are responsible for cellular mechanics. MPTM was developed as an approach to map intracellular mechanical properties of living cells and track the intracellular particles by Brownian motion to establish a viscoelastic model and compare it with the power-law approach. A quantification of the MPTM allowed capturing of the cell stiffness using the mean squared displacement (MSD) of cell under different conditions. The cytoskeletal elements actin and β-tubulin were analysed in qRT-PCR and Western blot as they form the key elements governing a cell’s mechanical stability and response to mechanical stimuli. The findings from this study revealed cell stiffness decreases as cancer progress, thereby cells become stiffer. The same pattern was evident for chemoresistant malignant cells and revealed that they had a loss of elasticity in comparison to their counter non-resistant malignant cells. With regards to protein levels and mRNA expression, the chemotherapeutic drug affected the cytoskeleton causing cells to undergo morphological changes which, however, was not seen in chemoresistant cells. The results from this study indicated that measuring mechanical properties of cells provides an efficient marker for cancer diagnosis and deeper understanding of cancer mechanobiology. Advisors/Committee Members: Franz, Thomas (advisor), Zaman, M (advisor), Prince, S (advisor).

Subjects/Keywords: Mechanobiology

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APA (6^th Edition):

Smith, R. (2019). Cancer Cell Mechanics in Chemoresistance and Chemotherapeutic Drug Exposure. (Masters Thesis). University of Cape Town. Retrieved from http://hdl.handle.net/11427/31268

Chicago Manual of Style (16^th Edition):

Smith, Rochelle. “Cancer Cell Mechanics in Chemoresistance and Chemotherapeutic Drug Exposure.” 2019. Masters Thesis, University of Cape Town. Accessed January 23, 2021. http://hdl.handle.net/11427/31268.

MLA Handbook (7^th Edition):

Smith, Rochelle. “Cancer Cell Mechanics in Chemoresistance and Chemotherapeutic Drug Exposure.” 2019. Web. 23 Jan 2021.

Vancouver:

Smith R. Cancer Cell Mechanics in Chemoresistance and Chemotherapeutic Drug Exposure. [Internet] [Masters thesis]. University of Cape Town; 2019. [cited 2021 Jan 23]. Available from: http://hdl.handle.net/11427/31268.

Council of Science Editors:

Smith R. Cancer Cell Mechanics in Chemoresistance and Chemotherapeutic Drug Exposure. [Masters Thesis]. University of Cape Town; 2019. Available from: http://hdl.handle.net/11427/31268

2. Yogurtcu, Osman. COMPUTATIONAL MECHANOBIOLOGY OF FILAMENTOUS PROTEINS: ALPHA-HELICAL COILED COILS AND F-ACTIN.

Degree: 2013, Johns Hopkins University

URL: http://jhir.library.jhu.edu/handle/1774.2/36991

► This dissertation sits at the intersection of mechanics and biology. Specifically, we devise mesoscopic mechanochemical models to study biofilaments, very ubiquitous cellular protein structures. Since… (more)

▼ This dissertation sits at the intersection of mechanics and biology. Specifically, we devise mesoscopic mechanochemical models to study biofilaments, very ubiquitous cellular protein structures. Since they undergo functional bending, twisting, buckling and stretching motions, understanding the mechanical response of biofilaments is crucial for a correct description of the conformational states of these proteins. Our models contribute to the better understanding of the nonlinearities in the mechanical response of biofilaments to the environmental perturbations, without resorting to computationally costly full atomistic simulations. Two important filamentous structures coiled-coil and actin make up the main concentration of our work. Coiled coils are a rope-like protein motif formed by two or more alpha helices. The energetic of a coiled coil involves a competition between elastic deformation and hydrophobic interaction of residues of each helix. The model treats alpha helices as elastic rods where each rod interacts with another exclusively through beads representing the hydrophobic residues. We validate our model using steered molecular dynamics simulations and compare it with continuum thin rod model. We analyze the bending, buckling and twisting behavior of coiled coil molecules of various lengths and conclude that a coiled coil molecule cannot be fully characterized by a simple single-parameter mechanical model. The second filamentous biological structure we study is filamentous actin, F-actin, which is an important player in eukaryotic cellular processes including motility, morphogenesis, and mechanosensation. Actin monomer, G-actin, polymerizes to form F-actin. G-actin is an ATP hydrolase and at any time it is bound to either an ATP or ADP molecule. Mechanical and chemical properties of actin filaments are strongly coupled to each other through the bound nucleotide type. In our model of F-actin, each monomer is treated as a spherical particle with a bound molecule identity. The particles are connected by a set of springs with changing mechanical properties that depend on the bound molecule. Using this model, we study and explain the behavior of actin filaments under various external mechanical stimuli introduced by actin binding proteins. Finally, we discuss the coupling of monomer chemical state changes to the global mechanical response of actin. Advisors/Committee Members: Sun, Sean X (advisor).

Subjects/Keywords: Biofilaments; Mechanobiology; Computational

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APA (6^th Edition):

Yogurtcu, O. (2013). COMPUTATIONAL MECHANOBIOLOGY OF FILAMENTOUS PROTEINS: ALPHA-HELICAL COILED COILS AND F-ACTIN. (Thesis). Johns Hopkins University. Retrieved from http://jhir.library.jhu.edu/handle/1774.2/36991

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Yogurtcu, Osman. “COMPUTATIONAL MECHANOBIOLOGY OF FILAMENTOUS PROTEINS: ALPHA-HELICAL COILED COILS AND F-ACTIN.” 2013. Thesis, Johns Hopkins University. Accessed January 23, 2021. http://jhir.library.jhu.edu/handle/1774.2/36991.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Yogurtcu, Osman. “COMPUTATIONAL MECHANOBIOLOGY OF FILAMENTOUS PROTEINS: ALPHA-HELICAL COILED COILS AND F-ACTIN.” 2013. Web. 23 Jan 2021.

Vancouver:

Yogurtcu O. COMPUTATIONAL MECHANOBIOLOGY OF FILAMENTOUS PROTEINS: ALPHA-HELICAL COILED COILS AND F-ACTIN. [Internet] [Thesis]. Johns Hopkins University; 2013. [cited 2021 Jan 23]. Available from: http://jhir.library.jhu.edu/handle/1774.2/36991.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Yogurtcu O. COMPUTATIONAL MECHANOBIOLOGY OF FILAMENTOUS PROTEINS: ALPHA-HELICAL COILED COILS AND F-ACTIN. [Thesis]. Johns Hopkins University; 2013. Available from: http://jhir.library.jhu.edu/handle/1774.2/36991

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Vanderbilt University

3. Chen, Joseph. The Mechanobiology of Notch1 Deficiency in Calcific Aortic Valve Disease.

Degree: PhD, Biomedical Engineering, 2015, Vanderbilt University

URL: http://hdl.handle.net/1803/10903

► Calcific aortic valve disease (CAVD) is the predominant valvular disease in the developed world, affecting over five million individuals in the United States alone and… (more)

▼ Calcific aortic valve disease (CAVD) is the predominant valvular disease in the developed world, affecting over five million individuals in the United States alone and manifests itself as a progressive disease resulting in the obstruction of left ventricular outflow, decreased cardiac output, and eventual heart failure. Presently, treatment for CAVD is limited to surgical aortic valve replacement, a high risk procedure especially for the population affected, and although significant advances have been made to reduce the associated risk with this procedure, a non-surgical treatment option is preferred. Unfortunately, current efforts to develop pharmacological treatments have been largely unsuccessful at preventing or slowing down the progression of CAVD; this lack of efficacy can be attributed to the incomplete understanding of the etiology of CAVD. Thus, focused attention must be placed on elucidating the underlying mechanisms of CAVD initiation and evolution in order to develop novel and effective pharmacological drugs. At the tissue level, normal supple leaflets are transformed into thickened, stiff, and calcified leaflets; these striking changes are attributed to the aberrant behavior of the resident cell population, the aortic valve interstitial cells (AVICs), which are believed to play significant roles in leaflet thickening and calcification. Investigating what factors contribute to AVIC differentiation into pathological phenotypes and further how they generate valvular calcification is essential to the understanding of CAVD etiology. It has been demonstrated that CAVD development is tightly regulated by biomolecular, mechanobiological, and genetic factors. Previous studies have focused on describing the effect of biomolecular cues on CN development; however, many mechanobiological and genetic factors that have significant in vivo relevance have not been thoroughly assessed. In an effort to gather insight towards CAVD processes in vivo, we believe that investigations into the role of mechanical strain and the effect of Notch1 mutation on AVIC biology and calcification would provide novel insights towards CAVD etiology that can contribute to the development of effect therapeutics. Advisors/Committee Members: H. Scott Baldwin (committee member), Christopher B. Brown (committee member), Michael I. Miga (committee member), Hak-Joon Sung (committee member), W. David Merryman (Committee Chair).

Subjects/Keywords: aortic valve; valvular disease; mechanobiology

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APA (6^th Edition):

Chen, J. (2015). The Mechanobiology of Notch1 Deficiency in Calcific Aortic Valve Disease. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/10903

Chicago Manual of Style (16^th Edition):

Chen, Joseph. “The Mechanobiology of Notch1 Deficiency in Calcific Aortic Valve Disease.” 2015. Doctoral Dissertation, Vanderbilt University. Accessed January 23, 2021. http://hdl.handle.net/1803/10903.

MLA Handbook (7^th Edition):

Chen, Joseph. “The Mechanobiology of Notch1 Deficiency in Calcific Aortic Valve Disease.” 2015. Web. 23 Jan 2021.

Vancouver:

Chen J. The Mechanobiology of Notch1 Deficiency in Calcific Aortic Valve Disease. [Internet] [Doctoral dissertation]. Vanderbilt University; 2015. [cited 2021 Jan 23]. Available from: http://hdl.handle.net/1803/10903.

Council of Science Editors:

Chen J. The Mechanobiology of Notch1 Deficiency in Calcific Aortic Valve Disease. [Doctoral Dissertation]. Vanderbilt University; 2015. Available from: http://hdl.handle.net/1803/10903

University of New South Wales

4. Govendir, Matt. Mechanobiology of Targeted Killing of Tumour Cells by Cytotoxic T Lymphocytes.

Degree: Medical Sciences, 2019, University of New South Wales

URL: http://handle.unsw.edu.au/1959.4/65517 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:64451/SOURCE02?view=true

► Cytotoxic T lymphocytes (CTLs) are killer cells of the adaptive immune system that patrol tissues in search of cancerous or virally infected cells. Following recognition… (more)

Subjects/Keywords: Cancer biology; Mechanobiology; Immunology

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APA (6^th Edition):

Govendir, M. (2019). Mechanobiology of Targeted Killing of Tumour Cells by Cytotoxic T Lymphocytes. (Doctoral Dissertation). University of New South Wales. Retrieved from http://handle.unsw.edu.au/1959.4/65517 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:64451/SOURCE02?view=true

Chicago Manual of Style (16^th Edition):

Govendir, Matt. “Mechanobiology of Targeted Killing of Tumour Cells by Cytotoxic T Lymphocytes.” 2019. Doctoral Dissertation, University of New South Wales. Accessed January 23, 2021. http://handle.unsw.edu.au/1959.4/65517 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:64451/SOURCE02?view=true.

MLA Handbook (7^th Edition):

Govendir, Matt. “Mechanobiology of Targeted Killing of Tumour Cells by Cytotoxic T Lymphocytes.” 2019. Web. 23 Jan 2021.

Vancouver:

Govendir M. Mechanobiology of Targeted Killing of Tumour Cells by Cytotoxic T Lymphocytes. [Internet] [Doctoral dissertation]. University of New South Wales; 2019. [cited 2021 Jan 23]. Available from: http://handle.unsw.edu.au/1959.4/65517 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:64451/SOURCE02?view=true.

Council of Science Editors:

Govendir M. Mechanobiology of Targeted Killing of Tumour Cells by Cytotoxic T Lymphocytes. [Doctoral Dissertation]. University of New South Wales; 2019. Available from: http://handle.unsw.edu.au/1959.4/65517 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:64451/SOURCE02?view=true

University of New South Wales

5. Ridone, Pietro. Modulation of mechanosensitive channel activity by plasma membrane lipids.

Degree: Victor Chang Cardiac Research Institute, 2019, University of New South Wales

URL: http://handle.unsw.edu.au/1959.4/62985 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:59526/SOURCE02?view=true

► Biological cells are sensitive to physical stimuli, however the mechanisms underlying this sensitivity are still poorly understood. The sensation and conversion of a physical stimulus… (more)

▼ Biological cells are sensitive to physical stimuli, however the mechanisms underlying this sensitivity are still poorly understood. The sensation and conversion of a physical stimulus into electrical and biochemical intracellular signalling, a process termed mechanosensory transduction (mechanotransduction), is mediated by a variety of membrane-bound proteins loosely referred to as mechanoreceptors or mechanotransducers. These encompass all the active and passive membrane components of the mechanotransductory process, including the extracellular matrix, cytoskeleton and crosslinking intermediate filaments, non-conductive membrane proteins, transporters, ion channels, chromatin and lastly, the plasma membrane itself. Biological membranes are essential structural components of living cells which encapsulate and compartmentalize the biochemical processes essential for life and act as a primary host for mechanoreceptors. A specific class of mechanoreceptors, the mechanosensitive (MS) ion channels, is responsible for the fast conversion of physical stimuli into ionic currents. Currently little is known about the role of membrane lipids in regulating the activity of mechanosensitive channels in humans. The following thesis aims to describe how specific membrane lipids can modulate the activity of tension-gated MS channels, focussing specifically on the eukaryotic channel PIEZO1. By employing a combination of patch-clamp electrophysiology and fluorescence microscopy techniques it was possible to characterize the effects of cholesterol and poly-unsaturated fatty acids on the function and localization of PIEZO1 in cultured human cells. Manipulation of membrane lipids produced dramatic effects on the sensitivity and kinetics of PIEZO1, an essential receptor of membrane tension involved in development and pathology. Furthermore, the observed effects could be recapitulated in minimal in vitro liposome systems where the purified PIEZO1 channel was reconstituted. This work demonstrates that altered lipid environments can impact on the functioning of PIEZO1 and can result in phenotypes reminiscent of mutant channel variants involved in pathology. This work furthers our understanding of the general principles behind the membrane dependence of the mechanosensory processes that govern many aspects of cellular life and will provide new insights on how cells regulate essential adaptive processes such as growth, movement and gene expression. Advisors/Committee Members: Martinac, Boris, Victor Chang Cardiac Research Institute, Faculty of Medicine, UNSW, Battle, Andrew, Queensland University of Technology, Hill, Adam, Victor Chang Cardiac Research Institute, Faculty of Medicine, UNSW.

Subjects/Keywords: Fluorescence microscopy; Mechanobiology; Electrophysiology

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APA (6^th Edition):

Ridone, P. (2019). Modulation of mechanosensitive channel activity by plasma membrane lipids. (Doctoral Dissertation). University of New South Wales. Retrieved from http://handle.unsw.edu.au/1959.4/62985 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:59526/SOURCE02?view=true

Chicago Manual of Style (16^th Edition):

Ridone, Pietro. “Modulation of mechanosensitive channel activity by plasma membrane lipids.” 2019. Doctoral Dissertation, University of New South Wales. Accessed January 23, 2021. http://handle.unsw.edu.au/1959.4/62985 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:59526/SOURCE02?view=true.

MLA Handbook (7^th Edition):

Ridone, Pietro. “Modulation of mechanosensitive channel activity by plasma membrane lipids.” 2019. Web. 23 Jan 2021.

Vancouver:

Ridone P. Modulation of mechanosensitive channel activity by plasma membrane lipids. [Internet] [Doctoral dissertation]. University of New South Wales; 2019. [cited 2021 Jan 23]. Available from: http://handle.unsw.edu.au/1959.4/62985 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:59526/SOURCE02?view=true.

Council of Science Editors:

Ridone P. Modulation of mechanosensitive channel activity by plasma membrane lipids. [Doctoral Dissertation]. University of New South Wales; 2019. Available from: http://handle.unsw.edu.au/1959.4/62985 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:59526/SOURCE02?view=true

University of California – Riverside

6. Yang, Xiao. Mechanical Control of Retinal Vascular Inflammation in Diabetes.

Degree: Bioengineering, 2016, University of California – Riverside

URL: http://www.escholarship.org/uc/item/1xp618nx

► The goal of this research was to understand the role of cell- and subendothelial matrix-dependent mechanical cues in retinal endothelial cell (EC) activation associated with… (more)

Subjects/Keywords: Biomedical engineering; Diabetic Retinopathy; Inflammation; Mechanobiology

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APA (6^th Edition):

Yang, X. (2016). Mechanical Control of Retinal Vascular Inflammation in Diabetes. (Thesis). University of California – Riverside. Retrieved from http://www.escholarship.org/uc/item/1xp618nx

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Yang, Xiao. “Mechanical Control of Retinal Vascular Inflammation in Diabetes.” 2016. Thesis, University of California – Riverside. Accessed January 23, 2021. http://www.escholarship.org/uc/item/1xp618nx.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Yang, Xiao. “Mechanical Control of Retinal Vascular Inflammation in Diabetes.” 2016. Web. 23 Jan 2021.

Vancouver:

Yang X. Mechanical Control of Retinal Vascular Inflammation in Diabetes. [Internet] [Thesis]. University of California – Riverside; 2016. [cited 2021 Jan 23]. Available from: http://www.escholarship.org/uc/item/1xp618nx.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Yang X. Mechanical Control of Retinal Vascular Inflammation in Diabetes. [Thesis]. University of California – Riverside; 2016. Available from: http://www.escholarship.org/uc/item/1xp618nx

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of California – San Diego

7. Plunkett, Christopher Michael. Modeling Mammary Tumor Invasion in Response to Changes in Matrix Stiffness.

Degree: Bioengineering, 2018, University of California – San Diego

URL: http://www.escholarship.org/uc/item/8854z28x

► The progression of mammary carcinoma involves a variety of cellular and environmental factors that facilitate invasion of the stroma. Stiffening of the extracellular matrix is… (more)

Subjects/Keywords: Bioengineering; Biomaterials; Breast Cancer; Mechanobiology; Metastasis

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APA (6^th Edition):

Plunkett, C. M. (2018). Modeling Mammary Tumor Invasion in Response to Changes in Matrix Stiffness. (Thesis). University of California – San Diego. Retrieved from http://www.escholarship.org/uc/item/8854z28x

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Plunkett, Christopher Michael. “Modeling Mammary Tumor Invasion in Response to Changes in Matrix Stiffness.” 2018. Thesis, University of California – San Diego. Accessed January 23, 2021. http://www.escholarship.org/uc/item/8854z28x.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Plunkett, Christopher Michael. “Modeling Mammary Tumor Invasion in Response to Changes in Matrix Stiffness.” 2018. Web. 23 Jan 2021.

Vancouver:

Plunkett CM. Modeling Mammary Tumor Invasion in Response to Changes in Matrix Stiffness. [Internet] [Thesis]. University of California – San Diego; 2018. [cited 2021 Jan 23]. Available from: http://www.escholarship.org/uc/item/8854z28x.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Plunkett CM. Modeling Mammary Tumor Invasion in Response to Changes in Matrix Stiffness. [Thesis]. University of California – San Diego; 2018. Available from: http://www.escholarship.org/uc/item/8854z28x

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Georgia Tech

8. Zhou, Dennis Wei. Force-signaling coupling at single focal adhesions.

Degree: PhD, Biomedical Engineering (Joint GT/Emory Department), 2019, Georgia Tech

URL: http://hdl.handle.net/1853/62651

► Integrin-mediated adhesion to extracellular matrices (ECM) provides forces and signals that direct cell processes central to tissue organization, homeostasis, and disease. Recent studies show an… (more)

▼ Integrin-mediated adhesion to extracellular matrices (ECM) provides forces and signals that direct cell processes central to tissue organization, homeostasis, and disease. Recent studies show an important relationship between cell adhesive force generation and focal adhesion (FA) assembly, yet it remains unclear how forces are transduced into adhesive signals. Our work seeks to identify coupling between cell adhesive force generation and signaling at FAs. To measure forces, we used Microfabricated Post-Array-Deflectors (mPADs), which are an array of PDMS ~1.8 µm diameter microposts. Based on the micropost deflections, we can calculate the forces exerted by cells. We previously showed that vinculin regulates force transmission at FAs. Vinculin residence time in FAs correlated with applied force, supporting a mechanosensitive model in which forces stabilize vinculin’s active conformation to promote force transfer. We first examined the relationship between traction force and vinculin-paxillin localization to single FAs in the context of substrate stiffness and actomyosin contractility. Substrate stiffness and contractility regulated vinculin localization to FAs, and vinculin auto-inhibition is a crucial regulatory step in this process that overrides the effects of cytoskeletal tension and substrate stiffness. Vinculin and paxillin FA area did not correlate with traction force magnitudes at single FAs, and this was consistent across different ECM stiffness and cytoskeletal tension states. Vinculin residence time at FAs linearly varied with applied force for stiff substrates, but this coupling was disrupted on soft substrates and in the presence of contractility inhibitors. In contrast, paxillin residence time at FAs was independent of force, substrate stiffness, and cytoskeletal contractility. Lastly, substrate stiffness and cytoskeletal contractility regulated whether vinculin and paxillin turnover dynamics are correlated to each other at single FAs. We also found that pFAK Y397 levels are linearly coupled to force at single FAs on stiff substrates. On soft substrates, however, this positive relationship is eliminated. We found that talin is required for FAK localization and Y397 phosphorylation at FAs and mediates force-FAK linear coupling at FAs via talin-FAK binding. Furthermore, averaged levels of FAK localization and Y397 phosphorylation at FAs are relatively insensitive to vinculin expression. However, a full-length vinculin molecule that binds talin and actin is required for linear coupling to occur between force-FAK localization and force-FAK Y397 phosphorylation at individual FAs. Lastly, we demonstrate that a full-length vinculin molecule that binds talin and actin is required to promote YAP nuclear accumulation. These findings suggest that force generation and signaling are coupled at FAs and underscore the role of environmental stiffness, talin, and vinculin in regulating force-signaling coupling at FAs. Our results generate new insights into how cell adhesive forces are integrated into biochemical signals.… Advisors/Committee Members: Garcia, Andres J. (advisor), Zhu, Cheng (committee member), Curtis, Jennifer E. (committee member), Kowalczyk, Andrew P. (committee member), del Campo, Aranzazu (committee member).

Subjects/Keywords: Focal adhesions; Mechanobiology; FAK; Mechanotransduction; Vinculin; YAP

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APA (6^th Edition):

Zhou, D. W. (2019). Force-signaling coupling at single focal adhesions. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/62651

Chicago Manual of Style (16^th Edition):

Zhou, Dennis Wei. “Force-signaling coupling at single focal adhesions.” 2019. Doctoral Dissertation, Georgia Tech. Accessed January 23, 2021. http://hdl.handle.net/1853/62651.

MLA Handbook (7^th Edition):

Zhou, Dennis Wei. “Force-signaling coupling at single focal adhesions.” 2019. Web. 23 Jan 2021.

Vancouver:

Zhou DW. Force-signaling coupling at single focal adhesions. [Internet] [Doctoral dissertation]. Georgia Tech; 2019. [cited 2021 Jan 23]. Available from: http://hdl.handle.net/1853/62651.

Council of Science Editors:

Zhou DW. Force-signaling coupling at single focal adhesions. [Doctoral Dissertation]. Georgia Tech; 2019. Available from: http://hdl.handle.net/1853/62651

University of Toronto

9. Beca, Bogdan. A Platform for High-throughput Mechanobiological Stimulation of Engineered Microtissues.

Degree: 2012, University of Toronto

URL: http://hdl.handle.net/1807/32525

►

While tissue-engineering approaches of heart valves have made great strides towards creating functional tissues in vitro, the instruments used, named bioreactors, cannot efficiently integrate multiple… (more)

Subjects/Keywords: bioreactor; high-throughput; mechanobiology; microtissues; 0541; 0548

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APA (6^th Edition):

Beca, B. (2012). A Platform for High-throughput Mechanobiological Stimulation of Engineered Microtissues. (Masters Thesis). University of Toronto. Retrieved from http://hdl.handle.net/1807/32525

Chicago Manual of Style (16^th Edition):

Beca, Bogdan. “A Platform for High-throughput Mechanobiological Stimulation of Engineered Microtissues.” 2012. Masters Thesis, University of Toronto. Accessed January 23, 2021. http://hdl.handle.net/1807/32525.

MLA Handbook (7^th Edition):

Beca, Bogdan. “A Platform for High-throughput Mechanobiological Stimulation of Engineered Microtissues.” 2012. Web. 23 Jan 2021.

Vancouver:

Beca B. A Platform for High-throughput Mechanobiological Stimulation of Engineered Microtissues. [Internet] [Masters thesis]. University of Toronto; 2012. [cited 2021 Jan 23]. Available from: http://hdl.handle.net/1807/32525.

Council of Science Editors:

Beca B. A Platform for High-throughput Mechanobiological Stimulation of Engineered Microtissues. [Masters Thesis]. University of Toronto; 2012. Available from: http://hdl.handle.net/1807/32525

10. APRILE, PAOLA. Unravelling the role of mechanical cues on the chondrogenic differentiation of stem cells.

Degree: School of Engineering. Discipline of Mechanical & Manuf. Eng, 2019, Trinity College Dublin

URL: http://hdl.handle.net/2262/91120

► The inability of adult articular cartilage to regenerate has motivated the development of tissue engineering strategies to repair cartilage defects before they progress to osteoarthritis.… (more)

▼ The inability of adult articular cartilage to regenerate has motivated the development of tissue engineering strategies to repair cartilage defects before they progress to osteoarthritis. Common cell based strategies employing autologous chondrocytes to treat cartilage lesions, often fail to promote hyaline cartilage repair. Mesenchymal stem cells / stromal cells (MSC) represent a promising cell type for cartilage tissue engineering, due to their relative ease of isolation, ability to proliferate extensively in vitro and differentiate along multiple pathways1-3. MSC differentiation can be influenced by the mechanical properties of their environment4. The objective of this dissertation was to examine the influence of intrinsic and extrinsic mechanical cues on the initiation of chondrogenesis of MSC seeded on top (2-Dimension) or encapsulated within (3-Dimension) hydrogels of defined stiffness. The development of an Interpenetrating Network (IPN) hydrogel system able to support cell growth in 2D and 3D, enabled the independent control of substrate rigidity (2D and 3D) and cell morphology (3D). A softer environment (2D and 3D) was correlated to enhanced upregulation of key chondrogenic markers and cell condensation. Contrary to the expectations, allowing the cells to spread in a soft 3D context greatly improved this chondrogenic response. Finally, the effect of biomaterial's mechanical properties and external forces was combined to the application of a physiological magnitude of Hydrostatic Pressure (HP) to mimic the physiological environment of a loaded knee joint. In this case, the chondrogenic differentiation of HP-stimulated cells resulted enhanced to a greater extent, when the mechanical perturbation was applied after the initiation of their chondrogenic commitment. Mechanical forces and local morphogen gradients greatly influence cartilage development, hence biomimetic cartilage repair strategies aiming to recapitulate the complex interplay of biophysical and biochemical cues, would open new possibilities for cartilage tissue regeneration5,6. The results described in this work evidenced the fundamental role of biophysical cues in regulating MSC biology and the importance of this information to inspire new biomimetic strategies for stem cell based cartilage regeneration procedures. REFERENCES 1. Johnstone, B., Hering, T. M., Caplan, A. I., Goldberg, V. M. & Yoo, J. U. In VitroChondrogenesis of Bone Marrow-Derived Mesenchymal Progenitor Cells. Exp. Cell Res. 238, 265-272 (1998). 2. Caplan, A. I. Mesenchymal stem cells. J. Orthop. Res. 9, 641-650 (1991). 3. Badylak, S. F., Weiss, D. J., Caplan, A. & Macchiarini, P. Engineered whole organs and complex tissues. Lancet 379, 943-52 (2012). 4. Engler, A. J., Sen, S., Sweeney, H. L. & Discher, D. E. Matrix Elasticity Directs Stem Cell Lineage Specification. Cell 126, 677-689 (2006). 5. Ingber, D. E. et al. Tissue Engineering and Developmental Biology: Going Biomimetic. Tissue Eng. 12, 3265-3283 (2007). 6. Mammoto, T., Mammoto, A. & Ingber, D. E. Mechanobiology and… Advisors/Committee Members: Kelly, Daniel.

Subjects/Keywords: Hydrostatic pressure; Mechanobiology; YAP; N-cadherin

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APA (6^th Edition):

APRILE, P. (2019). Unravelling the role of mechanical cues on the chondrogenic differentiation of stem cells. (Thesis). Trinity College Dublin. Retrieved from http://hdl.handle.net/2262/91120

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

APRILE, PAOLA. “Unravelling the role of mechanical cues on the chondrogenic differentiation of stem cells.” 2019. Thesis, Trinity College Dublin. Accessed January 23, 2021. http://hdl.handle.net/2262/91120.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

APRILE, PAOLA. “Unravelling the role of mechanical cues on the chondrogenic differentiation of stem cells.” 2019. Web. 23 Jan 2021.

Vancouver:

APRILE P. Unravelling the role of mechanical cues on the chondrogenic differentiation of stem cells. [Internet] [Thesis]. Trinity College Dublin; 2019. [cited 2021 Jan 23]. Available from: http://hdl.handle.net/2262/91120.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

APRILE P. Unravelling the role of mechanical cues on the chondrogenic differentiation of stem cells. [Thesis]. Trinity College Dublin; 2019. Available from: http://hdl.handle.net/2262/91120

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Delft University of Technology

11. Dahar, S. (author). A New Method For Fabrication of Medical Microfluidic Devices.

Degree: 2016, Delft University of Technology

URL: http://resolver.tudelft.nl/uuid:7b23edc2-9b42-4d4a-bca3-7bde6dfc0003

►

This thesis presents a fabrication process for medical microfluidic devices that is performed with purely silicon microfabrication methods, which is a better option for mass-production… (more)

Subjects/Keywords: Microfluids; Silicon microfabrication; Microfluidic devices; Cell mechanobiology

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APA (6^th Edition):

Dahar, S. (. (2016). A New Method For Fabrication of Medical Microfluidic Devices. (Masters Thesis). Delft University of Technology. Retrieved from http://resolver.tudelft.nl/uuid:7b23edc2-9b42-4d4a-bca3-7bde6dfc0003

Chicago Manual of Style (16^th Edition):

Dahar, S (author). “A New Method For Fabrication of Medical Microfluidic Devices.” 2016. Masters Thesis, Delft University of Technology. Accessed January 23, 2021. http://resolver.tudelft.nl/uuid:7b23edc2-9b42-4d4a-bca3-7bde6dfc0003.

MLA Handbook (7^th Edition):

Dahar, S (author). “A New Method For Fabrication of Medical Microfluidic Devices.” 2016. Web. 23 Jan 2021.

Vancouver:

Dahar S(. A New Method For Fabrication of Medical Microfluidic Devices. [Internet] [Masters thesis]. Delft University of Technology; 2016. [cited 2021 Jan 23]. Available from: http://resolver.tudelft.nl/uuid:7b23edc2-9b42-4d4a-bca3-7bde6dfc0003.

Council of Science Editors:

Dahar S(. A New Method For Fabrication of Medical Microfluidic Devices. [Masters Thesis]. Delft University of Technology; 2016. Available from: http://resolver.tudelft.nl/uuid:7b23edc2-9b42-4d4a-bca3-7bde6dfc0003

Princeton University

12. Beroz, Farzan. Mechanoperception and morphogenesis of living architectures .

Degree: PhD, 2018, Princeton University

URL: http://arks.princeton.edu/ark:/88435/dsp015m60qv60b

► In this thesis, we elucidate how living systems form and maintain their architectures by studying two systems that exemplify, respectively, the statical and dynamical properties… (more)

Subjects/Keywords: biofilms; biopolymers; disorder; mechanobiology; mechanosensing; networks

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APA (6^th Edition):

Beroz, F. (2018). Mechanoperception and morphogenesis of living architectures . (Doctoral Dissertation). Princeton University. Retrieved from http://arks.princeton.edu/ark:/88435/dsp015m60qv60b

Chicago Manual of Style (16^th Edition):

Beroz, Farzan. “Mechanoperception and morphogenesis of living architectures .” 2018. Doctoral Dissertation, Princeton University. Accessed January 23, 2021. http://arks.princeton.edu/ark:/88435/dsp015m60qv60b.

MLA Handbook (7^th Edition):

Beroz, Farzan. “Mechanoperception and morphogenesis of living architectures .” 2018. Web. 23 Jan 2021.

Vancouver:

Beroz F. Mechanoperception and morphogenesis of living architectures . [Internet] [Doctoral dissertation]. Princeton University; 2018. [cited 2021 Jan 23]. Available from: http://arks.princeton.edu/ark:/88435/dsp015m60qv60b.

Council of Science Editors:

Beroz F. Mechanoperception and morphogenesis of living architectures . [Doctoral Dissertation]. Princeton University; 2018. Available from: http://arks.princeton.edu/ark:/88435/dsp015m60qv60b

University of Notre Dame

13. Thomas A. Metzger. Experimental and Computational Investigation of Bone Marrow Mechanobiology</h1>.

Degree: Bioengineering, 2016, University of Notre Dame

URL: https://curate.nd.edu/show/mc87pn91r9x

► Bone is a metabolically active tissue that undergoes constant repair and remodeling, depending on its biochemical and biomechanical environment. Bone metabolism is partially controlled… (more)

▼ Bone is a metabolically active tissue that undergoes constant repair and remodeling, depending on its biochemical and biomechanical environment. Bone metabolism is partially controlled by mechanical cues, with higher loads causing net bone accretion and lower loads fostering bone loss via cell signaling. While the osteocyte is considered the primary mechanosensory cell in bone, the bone marrow provides a niche for a multitude of mechanosensitive cell types that may also play a role in maintaining bone health and bone marrow health and physiology. The characterization of trabecular bone marrow mechanics during whole bone loading has been difficult due to its location, surrounded by cortical bone or within the complex geometry of trabecular bone which has limited our understanding of the role of bone marrow mechanobiology. The goal of this dissertation research was to establish methods to assess the micromechanical environment of trabecular bone marrow and to apply these methods to investigate changes in bone marrow mechanobiology in disease. Fresh bone marrow was experimentally tested to identify an appropriate constitutive model. The properties were highly non-Newtonian, viscous and deteriorated with storage. Implementation of this constitutive model in simulations is computationally expensive due to the multiple physics. However, comparison of the fluid constitutive model to several alternative elastic and viscoelastic formulations indicated that the solid models could not capture the fluid behavior despite the high viscosity and low velocity gradients. Hence, a power-law fluid constitutive model was adopted for later simulations. To assess the mechanical environment of the bone marrow during whole bone loading, bone marrow pressure was measured experimentally. Six fresh porcine femora were loaded cyclically while pressure and load were monitored. The marrow pressure reached 5 kPa, and the pressure gradients reached 0.46 kPa/mm. Experimental pressure gradients were applied to microscale models. The models found that the shear stress within the marrow pore space in the range of 2 Pa. The potential to generate these levels of pressure gradients and shear stress was further verified by novel high-resolution fluid-structure interaction finite element simulations. The models showed that the pressure gradients measured during loading were consistent with fluid-structure interaction simulations, based on measured marrow properties. Simulations further illustrated that increased strain rate, bone marrow viscosity, and BV/TV increase the pressure and shear stress within the bone marrow. In order to investigate how the calculated marrow shear stress is translated to the cell level, multi-scale models were applied. At the cell-level, the marrow shear stress was amplified by 4 times due to localized cell adhesion. However, this effect was attenuated as the adipocyte content in the marrow increased. Finally, in the conclusion of this work, experimental and computational studies seek to further elucidate… Advisors/Committee Members: Glen L. Niebur, Research Director.

Subjects/Keywords: Osteoporosis; Bone Marrow; Mechanobiology; Whole-Bone Loading

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APA (6^th Edition):

Metzger, T. A. (2016). Experimental and Computational Investigation of Bone Marrow Mechanobiology</h1>. (Thesis). University of Notre Dame. Retrieved from https://curate.nd.edu/show/mc87pn91r9x

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Metzger, Thomas A.. “Experimental and Computational Investigation of Bone Marrow Mechanobiology</h1>.” 2016. Thesis, University of Notre Dame. Accessed January 23, 2021. https://curate.nd.edu/show/mc87pn91r9x.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Metzger, Thomas A.. “Experimental and Computational Investigation of Bone Marrow Mechanobiology</h1>.” 2016. Web. 23 Jan 2021.

Vancouver:

Metzger TA. Experimental and Computational Investigation of Bone Marrow Mechanobiology</h1>. [Internet] [Thesis]. University of Notre Dame; 2016. [cited 2021 Jan 23]. Available from: https://curate.nd.edu/show/mc87pn91r9x.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Metzger TA. Experimental and Computational Investigation of Bone Marrow Mechanobiology</h1>. [Thesis]. University of Notre Dame; 2016. Available from: https://curate.nd.edu/show/mc87pn91r9x

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Toronto

14. Middleton, Kevin. Microfluidic Techniques to perform more Physiologically Relevant Bone Flow Experiments.

Degree: PhD, 2017, University of Toronto

URL: http://hdl.handle.net/1807/80969

► Mechanical stimulation of bone has often been used to prevent and/or treat various bone mass disorders. Osteocytes, as the major bone mechanosensory cell, are critical… (more)

▼ Mechanical stimulation of bone has often been used to prevent and/or treat various bone mass disorders. Osteocytes, as the major bone mechanosensory cell, are critical in regulating these disorders through the expression of factors that control bone homeostasis. The current methodology to study how fluid mechanostimulation of osteocytes regulates other cells in vitro is through the use of parallel plate flow chambers (PPFCs). In these studies, osteocytes are seeded on glass slides and loaded into PPFCs. Flow is applied to the osteocytes, and conditioned medium is collected, which can then be applied to the other cells being investigated. However, this methodology lacks real-time and direct signaling between the cells, and loses low half-life signal interactions. Additionally, these large PPFCs lack dimensional physiological relevance, and are non-viable for primary osteocyte studies. These limitations, however, can be mitigated through the use of microfluidics and/or co-culture. In this thesis, we present microfluidic techniques to significantly improve the physiological relevance of in vitro osteocyte flow experiments. First, we developed a microfluidic co-culture device to investigate mechanoregulated osteocyte-osteoclast cross-talk. Specifically, we demonstrated that unstimulated osteocytes create an environment that is preferential for osteoclast precursor aggregation and differentiation. Furthermore, we observed increased osteocyte mechanosensitivity in co-culture with osteoclasts. Next, we investigated how platform dimensions and forces applied to the cells, independent of shear stress, can affect osteocyte mechanosensitivity. We determined that this sensitivity was due to differences in flow rates and drag forces applied to the cells. Finally, we fabricated a microfluidic pump that was capable of applying physiologically relevant oscillatory fluid flow and inducing osteocyte intracellular calcium responses within microchannels. This work highlights the need to translate osteocyte mechanobiology studies to more dimensionally/biochemically relevant platforms using microfluidic technologies. As well, this work has already led to the development of in vitro platforms investigating osteocyte mechanical regulation of bone metastasis. Advisors/Committee Members: You, Lidan, Biomedical Engineering.

Subjects/Keywords: Co-culture; Mechanobiology; Microfluidics; Osteoclasts; Osteocyte; 0379

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APA (6^th Edition):

Middleton, K. (2017). Microfluidic Techniques to perform more Physiologically Relevant Bone Flow Experiments. (Doctoral Dissertation). University of Toronto. Retrieved from http://hdl.handle.net/1807/80969

Chicago Manual of Style (16^th Edition):

Middleton, Kevin. “Microfluidic Techniques to perform more Physiologically Relevant Bone Flow Experiments.” 2017. Doctoral Dissertation, University of Toronto. Accessed January 23, 2021. http://hdl.handle.net/1807/80969.

MLA Handbook (7^th Edition):

Middleton, Kevin. “Microfluidic Techniques to perform more Physiologically Relevant Bone Flow Experiments.” 2017. Web. 23 Jan 2021.

Vancouver:

Middleton K. Microfluidic Techniques to perform more Physiologically Relevant Bone Flow Experiments. [Internet] [Doctoral dissertation]. University of Toronto; 2017. [cited 2021 Jan 23]. Available from: http://hdl.handle.net/1807/80969.

Council of Science Editors:

Middleton K. Microfluidic Techniques to perform more Physiologically Relevant Bone Flow Experiments. [Doctoral Dissertation]. University of Toronto; 2017. Available from: http://hdl.handle.net/1807/80969

University of Illinois – Urbana-Champaign

15. Ali, Muhammad Yakut. Cellular mechanosensitivity in vitro: cell-ECM, cell-cell, and cell-material interactions.

Degree: PhD, Theoretical & Applied Mechans, 2015, University of Illinois – Urbana-Champaign

URL: http://hdl.handle.net/2142/88240

► In recent years it has become increasingly evident that physical cues like mechanical micro-environment and geometry, in addition to bio-chemical factors, plays an important role… (more)

▼ In recent years it has become increasingly evident that physical cues like mechanical micro-environment and geometry, in addition to bio-chemical factors, plays an important role in regulating cell functionalities. Cancer cells also respond to 2D and 3D matrix stiffness in a complex manner using a coordinated, hierarchical mechano-chemical system composed of adhesion receptors and associated signal transduction membrane proteins, the cytoskeletal architecture, and molecular motors. Mechanosensitivity of different cancer cells in vitro are investigated primarily with immortalized human cancer cell lines or murine derived primary cells, not with primary human cancer cells. Hence, little is known about the mechanosensitivity of primary human colon cancer cells in vitro. In the first part of this dissertation, an optimized protocol is described that demonstrates the isolation of primary human colon cells from healthy and cancerous surgical human tissue samples. Isolated colon cells are then successfully cultured on soft (2 kPa stiffness) and stiff (10 kPa stiffness) polyacrylamide (PA) hydrogels and rigid polystyrene (~3.6 GPa stiffness) substrates functionalized by an extracellular matrix (fibronectin in this case). Fluorescent microbeads are embedded in soft gels near the cell culture surface, and traction assay is performed to assess cellular contractile stresses. Our findings suggest that both the healthy and tumor cells are mechanosensitive. Their average spread area increased with increase in substrate stiffness, and they displayed actin stress fibers and elongated focal adhesions on rigid polystyrene substrates only. Traction cytometry results on soft gels are the first experimental evidence that primary colon tumor cells can generate augmented traction compared to their healthy counterparts. In addition, the contrast between traction patterns and metastatic staging raises the possibility of introducing a potent biophysical marker of cancer metastasis with other molecular biomarkers. In the second part, we study the role of cell-cell adhesions on the substrate elasticity mediated metastasis-like phenotype (MLP) of human colon carcinoma (HCT-8) cells. HCT-8 cells on PA gels is an attractive in vitro biomaterial platform as they exhibit a dissociative, metastasis-like phenotype (MLP) when cultured on extra-cellular matrix (ECM) coated gels with appropriate mechanical stiffness (20–47 kPa), but not on very stiff (3.6 GPa) polystyrene substrates. We ask the question whether similar morphological transition occurs on cell-cell adhesion molecule, i.e., E-cadherin coated PA gels and if so, how the actin cytoskeleton and focal adhesions compare with ECM mediated response on gels. Experimental results suggest that MLP of HCT-8 cells on PA gels is independent of cell to gel adhesion in 2D in vitro culture. Finally, we challenge the classical readouts of cellular mechanosensing by examining cell response on soft biological gel, namely, collagen. Our results show that different types of fibroblasts can exhibit spread… Advisors/Committee Members: Saif, M. Taher A. (advisor), Saif, M. Taher A. (Committee Chair), Jasiuk, Iwona (committee member), Dunn, Alison C (committee member), Harley, Brendan A. (committee member).

Subjects/Keywords: Cell Mechanics; Mechanobiology; Cancer Metastasis; Substrate Elasticity

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APA (6^th Edition):

Ali, M. Y. (2015). Cellular mechanosensitivity in vitro: cell-ECM, cell-cell, and cell-material interactions. (Doctoral Dissertation). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/88240

Chicago Manual of Style (16^th Edition):

Ali, Muhammad Yakut. “Cellular mechanosensitivity in vitro: cell-ECM, cell-cell, and cell-material interactions.” 2015. Doctoral Dissertation, University of Illinois – Urbana-Champaign. Accessed January 23, 2021. http://hdl.handle.net/2142/88240.

MLA Handbook (7^th Edition):

Ali, Muhammad Yakut. “Cellular mechanosensitivity in vitro: cell-ECM, cell-cell, and cell-material interactions.” 2015. Web. 23 Jan 2021.

Vancouver:

Ali MY. Cellular mechanosensitivity in vitro: cell-ECM, cell-cell, and cell-material interactions. [Internet] [Doctoral dissertation]. University of Illinois – Urbana-Champaign; 2015. [cited 2021 Jan 23]. Available from: http://hdl.handle.net/2142/88240.

Council of Science Editors:

Ali MY. Cellular mechanosensitivity in vitro: cell-ECM, cell-cell, and cell-material interactions. [Doctoral Dissertation]. University of Illinois – Urbana-Champaign; 2015. Available from: http://hdl.handle.net/2142/88240

University of Toronto

16. Liu, Chao. Osteocyte Signalling in Response to Mechanical Loading after Physical Cellular Damage and Hyperglycemia.

Degree: PhD, 2016, University of Toronto

URL: http://hdl.handle.net/1807/73058

► Osteocytes are cells that reside in the mineralized bone matrix. They are the cells that sense mechanical loading on the bone; and respond by directing… (more)

▼ Osteocytes are cells that reside in the mineralized bone matrix. They are the cells that sense mechanical loading on the bone; and respond by directing biochemical signals to osteoclasts (for bone resorption) and osteoblast (for bone formation) to remodel the bone. However, it is unknown how mechanical forces affect signaling of osteocytes that are affected by physical damage and pathological chemical environment. In the bone, mechanical loading causes micro-cracks, which cause physical damage to osteocytes and initiate bone remodeling. However, the role of subsequent mechanical loading on osteocyte is unclear. In this study, we have developed an in vitro cell model to study the impact of mechanical loading on osteocytes with physical damage. This model re-created the spatial distribution of osteocyte and signals expression around micro-cracks as in vivo. The results showed that 1) subcellular physical damage upregulates remodeling signals in osteocytes at 24 hr after damage, 2) mechanical loading substantially upregulates these signals for remodeling in osteocytes with physical damage. Hydraulic pressure and fluid flow shear stress are two concurrent mechanical stimuli on osteocytes, since the fluid shear is driven by the pressure gradient in the interstitial fluid in bone. A new mechanical loading system was developed to apply the concurrent mechanical forces. The loading system was able to safely apply physiological loading magnitudes to cells cultured on glass slides. It was found that concurrent pressure and shear stress had an additive effect on the reduction of osteocyte apoptosis. High glucose concentration in diabetic patients has resulted in retarded bone accumulation, bone loss, and an elevated risk of bone fracture. Osteocyte sensitivity to mechanical loading could be a factor in this pathology. The hypothesis is that hyperglycemia suppresses the beneficial effects of fluid flow shear stress on osteocytes. We found that high glucose level abolished mechanical-loading-induced changes in osteocyte signals to regulate bone remodeling, while osmotic control medium having the same elevated osmolarity did not have significant effects. Elevated glucose levels in diabetic patients could have direct effects on osteocytes, adversely influencing osteocyte response to mechanical loading, consequently the bone remodeling process. Advisors/Committee Members: You, Lidan, Biomedical Engineering.

Subjects/Keywords: diabetes; mechanobiology; microdamage; osteocyte; pressure; shear; 0648

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APA (6^th Edition):

Liu, C. (2016). Osteocyte Signalling in Response to Mechanical Loading after Physical Cellular Damage and Hyperglycemia. (Doctoral Dissertation). University of Toronto. Retrieved from http://hdl.handle.net/1807/73058

Chicago Manual of Style (16^th Edition):

Liu, Chao. “Osteocyte Signalling in Response to Mechanical Loading after Physical Cellular Damage and Hyperglycemia.” 2016. Doctoral Dissertation, University of Toronto. Accessed January 23, 2021. http://hdl.handle.net/1807/73058.

MLA Handbook (7^th Edition):

Liu, Chao. “Osteocyte Signalling in Response to Mechanical Loading after Physical Cellular Damage and Hyperglycemia.” 2016. Web. 23 Jan 2021.

Vancouver:

Liu C. Osteocyte Signalling in Response to Mechanical Loading after Physical Cellular Damage and Hyperglycemia. [Internet] [Doctoral dissertation]. University of Toronto; 2016. [cited 2021 Jan 23]. Available from: http://hdl.handle.net/1807/73058.

Council of Science Editors:

Liu C. Osteocyte Signalling in Response to Mechanical Loading after Physical Cellular Damage and Hyperglycemia. [Doctoral Dissertation]. University of Toronto; 2016. Available from: http://hdl.handle.net/1807/73058

Georgia Tech

17. Rathan, Swetha. Aortic valve mechanobiology- role of altered hemodynamics in mediating aortic valve inflammation and calcification.

Degree: PhD, Chemical and Biomolecular Engineering, 2016, Georgia Tech

URL: http://hdl.handle.net/1853/58144

► Calcific aortic valve (AV) disease is a strong risk factor for cardiovascular related deaths and is a significant source of mortality worldwide, with the number… (more)

▼ Calcific aortic valve (AV) disease is a strong risk factor for cardiovascular related deaths and is a significant source of mortality worldwide, with the number of patients requiring AV surgery expected to increase from 250,000 to 850,000 by 2050. However, the molecular mechanisms underlying AV disease have not been well studied or understood. Further, identification of biomarkers that can be used to detect early stage AV disease is also understudied but vital to successfully preventing and/or treating AV disease. It was hypothesized that sclerosis, inflammation and calcification preferentially occurs in the fibrosa compared to the ventricularis due to differential gene expression and oscillatory shear stress. Freshly isolated porcine AV leaflets and an ex vivo shear stress bioreactor was used to test this hypothesis. The low magnitude oscillatory shear stress (OS) appeared to predispose fibrosa to side-dependent calcification via increasing collagen turnover (Col1a1), and thickening of the extracellular matrix (ECM) (fibrosis) and decreasing the expression of genes that protect endothelial function (Klf4 and Enos). The unidirectional pulsatile shear, LS, however, preserved the ECM and gene expression in the ventricularis. The involvement of miRNAs in OS mediated AV pathogenesis was also investigated in a shear- and side-dependent manner. The miR-214 was found to play a role in this OS induced pathogenesis in fibrosa but not ventricularis. Using an ex vivo miRNA silencing protocol, anti-miRNA was delivered to both endothelial and interstitial cells of the AV tissue without compromising the cell viability. Silencing of miR-214 showed that the OS induced pathology in the fibrosa is likely to be mediated via miR-214, klf4 and Tgfβ1 dependent pathway that can lead to AV fibrosis, endothelial-to-mesenchymal transition and eventually sclerosis. The miR-214, however, did not play a role in shear-induced inflammation and calcification. The miR-214, as such, is likely to play a key role in the early onset of side- and shear- dependent AV disease and has a potential to serve as a disease biomarker. Further, an ex vivo AV calcification model was also developed to understand the role of endogenous pro- and anti-calcification factors, such as inorganic pyrophosphate, orthophosphate, and alkaline phosphatase. The functional studies carried out in this dissertation aim to link the mechanosensitive miRNAs to the genes involved in inflammation, endothelial-to-mesenchymal transition, and cell apoptosis etc, which eventually causes AV leaflets to calcify. Thus improved understanding of AV disease mechanisms under different hemodynamic conditions will enable us to improve the design of tissue-engineered valves and develop non-surgical treatment options. Advisors/Committee Members: Yoganathan, Ajit P. (advisor), Jo, Hanjoong (committee member), Taylor, W. Robert (committee member), Champion, Julie A. (committee member), Nerem, Robert M. (committee member).

Subjects/Keywords: Aortic valve; Hemodynamics; Mechanobiology; MicroRNA; Calcification

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APA (6^th Edition):

Rathan, S. (2016). Aortic valve mechanobiology- role of altered hemodynamics in mediating aortic valve inflammation and calcification. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/58144

Chicago Manual of Style (16^th Edition):

Rathan, Swetha. “Aortic valve mechanobiology- role of altered hemodynamics in mediating aortic valve inflammation and calcification.” 2016. Doctoral Dissertation, Georgia Tech. Accessed January 23, 2021. http://hdl.handle.net/1853/58144.

MLA Handbook (7^th Edition):

Rathan, Swetha. “Aortic valve mechanobiology- role of altered hemodynamics in mediating aortic valve inflammation and calcification.” 2016. Web. 23 Jan 2021.

Vancouver:

Rathan S. Aortic valve mechanobiology- role of altered hemodynamics in mediating aortic valve inflammation and calcification. [Internet] [Doctoral dissertation]. Georgia Tech; 2016. [cited 2021 Jan 23]. Available from: http://hdl.handle.net/1853/58144.

Council of Science Editors:

Rathan S. Aortic valve mechanobiology- role of altered hemodynamics in mediating aortic valve inflammation and calcification. [Doctoral Dissertation]. Georgia Tech; 2016. Available from: http://hdl.handle.net/1853/58144

Georgia Tech

18. Bachman, Haylee N. Exploring fibronectin's integrin binding domain effects on lung fibroblast integrin specificity and downstream phenotypic differences.

Degree: PhD, Chemistry and Biochemistry, 2017, Georgia Tech

URL: http://hdl.handle.net/1853/60669

► Recombinant proteins which mimic fibronectin’s (Fn’s) integrin binding domain in conformationally stable and unfolded states are investigated to explore integrin specificity and downstream phenotypic differences… (more)

Subjects/Keywords: Fibronectin; Integrin; Mechanobiology; Matrix biology; Extracellular matrix

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APA (6^th Edition):

Bachman, H. N. (2017). Exploring fibronectin's integrin binding domain effects on lung fibroblast integrin specificity and downstream phenotypic differences. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/60669

Chicago Manual of Style (16^th Edition):

Bachman, Haylee N. “Exploring fibronectin's integrin binding domain effects on lung fibroblast integrin specificity and downstream phenotypic differences.” 2017. Doctoral Dissertation, Georgia Tech. Accessed January 23, 2021. http://hdl.handle.net/1853/60669.

MLA Handbook (7^th Edition):

Bachman, Haylee N. “Exploring fibronectin's integrin binding domain effects on lung fibroblast integrin specificity and downstream phenotypic differences.” 2017. Web. 23 Jan 2021.

Vancouver:

Bachman HN. Exploring fibronectin's integrin binding domain effects on lung fibroblast integrin specificity and downstream phenotypic differences. [Internet] [Doctoral dissertation]. Georgia Tech; 2017. [cited 2021 Jan 23]. Available from: http://hdl.handle.net/1853/60669.

Council of Science Editors:

Bachman HN. Exploring fibronectin's integrin binding domain effects on lung fibroblast integrin specificity and downstream phenotypic differences. [Doctoral Dissertation]. Georgia Tech; 2017. Available from: http://hdl.handle.net/1853/60669

19. Nichols, Anne Elizabeth Carmack. Scleraxis-mediated regulation of tendon and ligament cell mechanobiology.

Degree: PhD, Biomedical and Veterinary Sciences, 2018, Virginia Tech

URL: http://hdl.handle.net/10919/86631

► Tendon and ligament injuries are common orthopedic problems that have an enormous impact on the quality of life of affected patients. Despite the frequency at… (more)

▼ Tendon and ligament injuries are common orthopedic problems that have an enormous impact on the quality of life of affected patients. Despite the frequency at which these injuries occur, current treatments are unable to restore native function to the damaged tissue. Because of this, reinjury is common. It is well known that mechanical stimulation is beneficial for promoting tendon and ligament development and tissue homeostasis; however, the specific mechanisms remain unclear. The transcription factor scleraxis (Scx) is an interesting candidate for mediating the tendon and ligament mechanoresponse, as it has been shown that Scx expression is induced by cyclic mechanical strain in tenocytes and is required for mechanically-induced stem cell tenogenesis. Moreover, Scx expression is increased in adult tendons following exercise. The studies described in this dissertation therefore focus on the combined role of Scx and mechanical stimulation in two contexts: 1) influencing ligament cell differentiation and 2) regulating adult tenocyte behavior. In the first study, transient Scx overexpression combined with mechanical strain in a 3D collagen hydrogel model was investigated as a means of deriving mature ligament cells from stem cells for use in ligament tissue engineering. Scx overexpression in C3H10T1/2 cells cultured in collagen hydrogels under static strain resulted in increased construct contraction and cell elongation, but no concurrent increase in the expression of ligament-related genes or production of glycosaminoglycans (GAG). When combined with low levels of cyclic strain, Scx overexpression resulted in increased mechanical properties of the tissue constructs, increased GAG production, and increased expression of ligament-related genes compared to cyclic strain alone. Together, these results demonstrate that Scx overexpression combined with cyclic strain can induce ligament cell differentiation and suggest that Scx does so by improving the mechanosensitivity of cells to cyclic strain. In the second study, the role of Scx in adult tenocyte mechanotransduction was explored using RNA-sequencing (RNA-seq) and small interfering RNA (siRNA) technologies. Equine tenocytes were exposed to siRNA targeting Scx or a control siRNA and maintained under cyclic mechanical strain prior to being submitted for RNA-seq. Comparison of the resulting transcriptomes revealed that Scx knockdown decreased the expression of several genes encoding important focal adhesion adaptor proteins. Correspondingly, Scx-depleted tenocytes showed abnormally long focal adhesions, decreased cytoskeletal stiffness, and an impaired ability to migrate on soft surfaces. This suggests that Scx regulates the tenocyte mechanoresponse by promoting the expression of focal adhesion-related genes. Combined, the results of these studies support a role for Scx in tendon and ligament cell mechanotransduction and identify the regulation of genes related to maintaining the cell-extracellular matrix connection and cytoskeletal dynamics as a… Advisors/Committee Members: Dahlgren, Linda A. (committeechair), Johnson, Sally E. (committee member), Whittington, Abby R. (committee member), Harris, Thurl E. (committee member).

Subjects/Keywords: mechanobiology; regenerative medicine; tissue engineering; tendon; ligament

10 more images…

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APA (6^th Edition):

Nichols, A. E. C. (2018). Scleraxis-mediated regulation of tendon and ligament cell mechanobiology. (Doctoral Dissertation). Virginia Tech. Retrieved from http://hdl.handle.net/10919/86631

Chicago Manual of Style (16^th Edition):

Nichols, Anne Elizabeth Carmack. “Scleraxis-mediated regulation of tendon and ligament cell mechanobiology.” 2018. Doctoral Dissertation, Virginia Tech. Accessed January 23, 2021. http://hdl.handle.net/10919/86631.

MLA Handbook (7^th Edition):

Nichols, Anne Elizabeth Carmack. “Scleraxis-mediated regulation of tendon and ligament cell mechanobiology.” 2018. Web. 23 Jan 2021.

Vancouver:

Nichols AEC. Scleraxis-mediated regulation of tendon and ligament cell mechanobiology. [Internet] [Doctoral dissertation]. Virginia Tech; 2018. [cited 2021 Jan 23]. Available from: http://hdl.handle.net/10919/86631.

Council of Science Editors:

Nichols AEC. Scleraxis-mediated regulation of tendon and ligament cell mechanobiology. [Doctoral Dissertation]. Virginia Tech; 2018. Available from: http://hdl.handle.net/10919/86631

Georgia Tech

20. Klosterhoff, Brett S. Mechanobiological Regulation of Early Stage Bone Repair.

Degree: PhD, Mechanical Engineering, 2019, Georgia Tech

URL: http://hdl.handle.net/1853/63531

► Each year in the United States alone, several hundred thousand people suffer skeletal fractures that do not heal from the original treatment, resulting in non-union.… (more)

▼ Each year in the United States alone, several hundred thousand people suffer skeletal fractures that do not heal from the original treatment, resulting in non-union. To improve patient outcomes, there is a clinical need for therapeutic strategies that stimulate bone repair. The skeleton dynamically adapts its structure and composition to mechanical loads, and controlled loading via rehabilitation represents a non-pharmacologic target with the potential to stimulate endogenous bone regeneration. The primary objectives of this thesis were to develop technical approaches to longitudinally monitor dynamic mechanical cues during bone healing and elucidate how specific magnitudes promote repair. Our overall hypothesis was that moderate mechanical stimulation exerted via periodic walking could enhance bone regeneration. To test this hypothesis, we engineered a fully implantable wireless strain sensor platform that enabled real-time non-invasive monitoring of mechanical cues in a pre-clinical model of skeletal repair. We discovered that early-stage strain magnitudes correlated with significantly improved healing outcomes. We also observed that osteogenic mechanical loading exerted effects on early stage biological processes that precede mineralization, including immune cytokine signaling and angiogenesis. At the conclusion of the experiments, we attained a deeper understanding of how specific mechanical cues regulate bone repair, and established a novel sensor platform to further investigate mechanobiology. The knowledge gained by this thesis aids the development of integrative therapeutic strategies that stimulate bone repair via functional rehabilitation. In addition, the technological outcomes of this thesis serve as foundational support for the expanded development of implantable medical sensor technologies with broad implications to enhance diagnostics, therapeutic development, and interventional surveillance. Advisors/Committee Members: Guldberg, Robert E (advisor), Willett, Nick J (advisor), Botchwey, Edward A (committee member), Ong, Keat Ghee (committee member), Hollister, Scott J (committee member), Weiss, Jeffrey A (committee member).

Subjects/Keywords: bone regeneration; biomedical sensors; mechanobiology; rehabilitation

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APA (6^th Edition):

Klosterhoff, B. S. (2019). Mechanobiological Regulation of Early Stage Bone Repair. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/63531

Chicago Manual of Style (16^th Edition):

Klosterhoff, Brett S. “Mechanobiological Regulation of Early Stage Bone Repair.” 2019. Doctoral Dissertation, Georgia Tech. Accessed January 23, 2021. http://hdl.handle.net/1853/63531.

MLA Handbook (7^th Edition):

Klosterhoff, Brett S. “Mechanobiological Regulation of Early Stage Bone Repair.” 2019. Web. 23 Jan 2021.

Vancouver:

Klosterhoff BS. Mechanobiological Regulation of Early Stage Bone Repair. [Internet] [Doctoral dissertation]. Georgia Tech; 2019. [cited 2021 Jan 23]. Available from: http://hdl.handle.net/1853/63531.

Council of Science Editors:

Klosterhoff BS. Mechanobiological Regulation of Early Stage Bone Repair. [Doctoral Dissertation]. Georgia Tech; 2019. Available from: http://hdl.handle.net/1853/63531

University of Pennsylvania

21. Bade, Nathan Donald. Pattern Formation By Cells On Curved Surfaces.

Degree: 2018, University of Pennsylvania

URL: https://repository.upenn.edu/edissertations/2948

► Cells have evolved sophisticated molecular machinery and signaling pathways to sense and respond to their environment. In particular, membrane receptor interactions with ligands immobilized on… (more)

▼ Cells have evolved sophisticated molecular machinery and signaling pathways to sense and respond to their environment. In particular, membrane receptor interactions with ligands immobilized on structures in the cells’ milieu allow them to sense the geometry of their surroundings, including the presence of surfaces or boundaries. In vivo, cells interact with curved surfaces with radii of curvature ranging from the size of a cell (50-100 microns) to millimeters; examples occur throughout the body in the form of vasculature, glands, and villi. However, remarkably little is known about cell interaction with non-planar boundaries; this dissertation probes how surface curvature influences cell alignment, internal microstructure, and migration. In the first study, mouse embryonic fibroblasts (MEFs) were cultured on glass cylinders with radii ranging from 40-200 µm. Isolated cells aligned along the axial direction on small cylinders but not large cylinders. Two distinct populations of actin stress fibers (SFs) aligned along the principal directions of the cylindrical surface: Long apical SFs spanned the nucleus and aligned along the axial direction whereas short, basal SFs beneath the nucleus aligned in the circumferential direction on small cylinders. The second study explored how these SF populations align on surfaces with non-zero Gaussian curvature. For this study, a sphere-with-skirt (SWS) surface was designed that seamlessly connects a positive Gaussian curvature spherical cap to a negative Gaussian curvature skirt. On the skirt, the SF populations again aligned along the principal directions: Apical SFs remained straight by forming chords over the concave gap and basal SFs bent along the convex direction. MEFs avoided the positive Gaussian curvature cap and instead migrated around the SWS feature in the azimuthal direction. Finally, the importance of edges between ligand-presenting and ligand-free domains was studied to discern the impact on cell alignment and migration. Edges enhanced the migration of isolated MEFs and acted as a slip boundary for cells in confluent, nematic monolayers. Topological defects emerged in corners where two edges met. These studies revealed that geometric cues in the form of surface curvature and bounding edges dictate cell alignment, cytoskeletal organization, and migration.

Subjects/Keywords: Cytoskeleton; Mechanobiology; Pattern formation; Biomechanics; Biophysics

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APA (6^th Edition):

Bade, N. D. (2018). Pattern Formation By Cells On Curved Surfaces. (Thesis). University of Pennsylvania. Retrieved from https://repository.upenn.edu/edissertations/2948

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Bade, Nathan Donald. “Pattern Formation By Cells On Curved Surfaces.” 2018. Thesis, University of Pennsylvania. Accessed January 23, 2021. https://repository.upenn.edu/edissertations/2948.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Bade, Nathan Donald. “Pattern Formation By Cells On Curved Surfaces.” 2018. Web. 23 Jan 2021.

Vancouver:

Bade ND. Pattern Formation By Cells On Curved Surfaces. [Internet] [Thesis]. University of Pennsylvania; 2018. [cited 2021 Jan 23]. Available from: https://repository.upenn.edu/edissertations/2948.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Bade ND. Pattern Formation By Cells On Curved Surfaces. [Thesis]. University of Pennsylvania; 2018. Available from: https://repository.upenn.edu/edissertations/2948

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Pennsylvania

22. Cao, Xuan. Continuum Modeling Of Cell-Extracellular Environment Interaction.

Degree: 2019, University of Pennsylvania

URL: https://repository.upenn.edu/edissertations/3477

► To perform functions such as proliferation, differentiation, and locomotion, living cells establish stable attachments to the extracellular matrix (ECM) via the formation of specialized receptor… (more)

Subjects/Keywords: Computational Biomechanics; Mechanobiology; Biophysics; Mechanics of Materials

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APA (6^th Edition):

Cao, X. (2019). Continuum Modeling Of Cell-Extracellular Environment Interaction. (Thesis). University of Pennsylvania. Retrieved from https://repository.upenn.edu/edissertations/3477

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Cao, Xuan. “Continuum Modeling Of Cell-Extracellular Environment Interaction.” 2019. Thesis, University of Pennsylvania. Accessed January 23, 2021. https://repository.upenn.edu/edissertations/3477.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Cao, Xuan. “Continuum Modeling Of Cell-Extracellular Environment Interaction.” 2019. Web. 23 Jan 2021.

Vancouver:

Cao X. Continuum Modeling Of Cell-Extracellular Environment Interaction. [Internet] [Thesis]. University of Pennsylvania; 2019. [cited 2021 Jan 23]. Available from: https://repository.upenn.edu/edissertations/3477.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Cao X. Continuum Modeling Of Cell-Extracellular Environment Interaction. [Thesis]. University of Pennsylvania; 2019. Available from: https://repository.upenn.edu/edissertations/3477

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Dalhousie University

23. Schwartz, Rachael. Development of a MEMS Device for the Determination of Cell Mechanics.

Degree: Master of Applied Science, Department of Mechanical Engineering, 2012, Dalhousie University

URL: http://hdl.handle.net/10222/15768

► Cell mechanics are directly related to the biological functionality of a cell, and therefore have been extensively studied. Current understanding of the unique relationships associated… (more)

Subjects/Keywords: Cell Mechanics; Mechanobiology; Measurement System; Micro-Electro Mechanical Systems

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APA (6^th Edition):

Schwartz, R. (2012). Development of a MEMS Device for the Determination of Cell Mechanics. (Masters Thesis). Dalhousie University. Retrieved from http://hdl.handle.net/10222/15768

Chicago Manual of Style (16^th Edition):

Schwartz, Rachael. “Development of a MEMS Device for the Determination of Cell Mechanics.” 2012. Masters Thesis, Dalhousie University. Accessed January 23, 2021. http://hdl.handle.net/10222/15768.

MLA Handbook (7^th Edition):

Schwartz, Rachael. “Development of a MEMS Device for the Determination of Cell Mechanics.” 2012. Web. 23 Jan 2021.

Vancouver:

Schwartz R. Development of a MEMS Device for the Determination of Cell Mechanics. [Internet] [Masters thesis]. Dalhousie University; 2012. [cited 2021 Jan 23]. Available from: http://hdl.handle.net/10222/15768.

Council of Science Editors:

Schwartz R. Development of a MEMS Device for the Determination of Cell Mechanics. [Masters Thesis]. Dalhousie University; 2012. Available from: http://hdl.handle.net/10222/15768

Dalhousie University

24. Walker, Matthew. The Development of a 3D Piezoelectric Active Microtissue Model for Airway Smooth Muscle.

Degree: Master of Applied Science, Department of Biomedical Engineering, 2013, Dalhousie University

URL: http://hdl.handle.net/10222/21862

► Although asthma is primarily thought to be an inflammatory disease of the airways, it has recently been hypothesized that the altered mechanical environment of an… (more)

Subjects/Keywords: Microtisse; Piezoelectric; 3D Cell Culture; Airway Smooth Muscle; Stretch; Asthma; Mechanobiology

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APA (6^th Edition):

Walker, M. (2013). The Development of a 3D Piezoelectric Active Microtissue Model for Airway Smooth Muscle. (Masters Thesis). Dalhousie University. Retrieved from http://hdl.handle.net/10222/21862

Chicago Manual of Style (16^th Edition):

Walker, Matthew. “The Development of a 3D Piezoelectric Active Microtissue Model for Airway Smooth Muscle.” 2013. Masters Thesis, Dalhousie University. Accessed January 23, 2021. http://hdl.handle.net/10222/21862.

MLA Handbook (7^th Edition):

Walker, Matthew. “The Development of a 3D Piezoelectric Active Microtissue Model for Airway Smooth Muscle.” 2013. Web. 23 Jan 2021.

Vancouver:

Walker M. The Development of a 3D Piezoelectric Active Microtissue Model for Airway Smooth Muscle. [Internet] [Masters thesis]. Dalhousie University; 2013. [cited 2021 Jan 23]. Available from: http://hdl.handle.net/10222/21862.

Council of Science Editors:

Walker M. The Development of a 3D Piezoelectric Active Microtissue Model for Airway Smooth Muscle. [Masters Thesis]. Dalhousie University; 2013. Available from: http://hdl.handle.net/10222/21862

University of California – Riverside

25. Maldonado, Maricela. Regulation of the Mechanical Niche to Guide Pluripotent Stem Cell Behaviors.

Degree: Bioengineering, 2016, University of California – Riverside

URL: http://www.escholarship.org/uc/item/1b8961wb

► The derivation of human induced pluripotent stem cells (IPSCs) has revolutionized the field of personalized medicine. With their ability to self-renew and differentiate to all… (more)

▼ The derivation of human induced pluripotent stem cells (IPSCs) has revolutionized the field of personalized medicine. With their ability to self-renew and differentiate to all cell types of the adult body, their therapeutic potential for multiple diseases is invaluable. Albeit their therapeutic potential is promising, they pose the risk of uncontrolled differentiation or tumorigenesis. Physical forces in the developing embryo have been shown to play a critical role in driving lineage commitment to regulate tissue morphogenesis. In this regard, the current work focused on examining the effects of the mechanical microenvironment, using electrospun scaffolds, on the cellular behaviors of human IPSCs. We examined the role of scaffold stiffness on the (1) self-renewal and (2) directed differentiation of IPSCs. Our findings demonstrate that the mechanical microenvironment contributes to the development of distinct IPSC colony morphology. Under proliferation conditions, a two-dimensional (2D) colony morphology on stiff scaffolds enhances proliferation and minimizes spontaneous differentiation of IPSCs. In contrast, the development of three-dimensional (3D) colonies on soft scaffolds results in increased spontaneous differentiation towards ectodermal lineage. Additionally, the development of distinct colonies, directed differentiation to mesendodermal lineage is enhanced on stiff scaffolds while ectodermal differentiation is enhanced on soft scaffolds. Furthermore, we demonstrate that modulation of the RhoA signaling pathway by scaffold stiffness or using a ROCK inhibitor can prime IPSCs to differentiate towards a mesendodermal lineage. We further demonstrate that actin and E-cadherin/β-catenin clustering mediates structural pre-stresses imposed on the cells, which may delay activation of the Wnt signaling pathway, as a result of developing 3D colony morphologies. Finally, we demonstrate that modulation of the scaffold stiffness, at each developmental stage of differentiation towards three germ layer derivate cell phenotypes, can enhance the differentiation of IPSCs. Overall, these findings demonstrate that IPSCs are mechano-responsive and that the mechanical niche can be designed to modulate IPSC behaviors for the control of differentiation or to study developmental processes in vitro.

Subjects/Keywords: Biomedical engineering; Cellular biology; differentiation; mechanobiology; pluripotent stem cells; self-renewal

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APA (6^th Edition):

Maldonado, M. (2016). Regulation of the Mechanical Niche to Guide Pluripotent Stem Cell Behaviors. (Thesis). University of California – Riverside. Retrieved from http://www.escholarship.org/uc/item/1b8961wb

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Maldonado, Maricela. “Regulation of the Mechanical Niche to Guide Pluripotent Stem Cell Behaviors.” 2016. Thesis, University of California – Riverside. Accessed January 23, 2021. http://www.escholarship.org/uc/item/1b8961wb.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Maldonado, Maricela. “Regulation of the Mechanical Niche to Guide Pluripotent Stem Cell Behaviors.” 2016. Web. 23 Jan 2021.

Vancouver:

Maldonado M. Regulation of the Mechanical Niche to Guide Pluripotent Stem Cell Behaviors. [Internet] [Thesis]. University of California – Riverside; 2016. [cited 2021 Jan 23]. Available from: http://www.escholarship.org/uc/item/1b8961wb.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Maldonado M. Regulation of the Mechanical Niche to Guide Pluripotent Stem Cell Behaviors. [Thesis]. University of California – Riverside; 2016. Available from: http://www.escholarship.org/uc/item/1b8961wb

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of California – San Diego

26. Hsu, Felix. ARTICULATION OF HUMAN ARTICULAR CARTILAGE INDUCES ANISOTROPIC STRUCTURAL DETERIORATION AND AGE-DEPENDENT CELLULAR RESPONSES.

Degree: Materials Sci and Engineering, 2017, University of California – San Diego

URL: http://www.escholarship.org/uc/item/7f51r8cd

► Articulation (shear and sliding) has been increasingly studied during the last two decades with the realization of its substantial involvement in daily locomotion of the… (more)

▼ Articulation (shear and sliding) has been increasingly studied during the last two decades with the realization of its substantial involvement in daily locomotion of the human knee joint. Conventional biological responses of mechanical stimulation on chondrocyte viability has been studied for shear and sliding; but in addition, the close relationship between articulation and lubrication has emphasized the importance of cell-mediated expression of the key boundary lubricating protein proteoglycan 4 (PRG4). While, in the absent of lubrication, shear and sliding between abnormal congruency between joint surfaces can initiate spatially-varied early degeneration, both instantly by direct mechanical damage of the cartilage and through time by mechanobiology. Thus, the overall motivation of this dissertation was to understand the effect of articulation (shear and sliding) on maintaining joint health as well as causing early or progressed degeneration in human articular cartilage.Spatially-oriented histopathological features were identified in cartilage lesions of human knee medial femoral condyles (MFCs) using a standardized, reliable grading system developed from primary literature, supporting the concept of mechanical articulation-driven cartilage deterioration. To recapitulate in vivo effects of articulation on human articular cartilage, human cartilage explants were subjected to mid to high amplitudes of articulation that can potentially stimulate chondrocyte response and cause matrix damage. Although articulation on cartilage explants induced superficial zone cell death and apoptosis (regardless of aging), only young and not old cartilage responded by secreting higher levels of PRG4 lubricant and continuously expressed enhanced levels of autophagy. However, the articulation regime applied in the absence of lubrication was insufficient to generate noticeable wear at the cartilage surface.Elucidating the mechanobiology of early degeneration in human articular cartilage by assessing the effects of articulation (shear and sliding) on SZ chondrocyte response and the initiation of matrix damage is one step towards a systems-based understanding of synovial joint homeostasis and derangement in health, aging, and disease. Furthermore, understanding the mechanobiological environments that can initiate cartilage degeneration can be critical to the development of preventive therapies for osteoarthritis.

Subjects/Keywords: Biomedical engineering; Biology; Aging; Articulation; Cartilage; Histopathology; Human knee joint; Mechanobiology

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APA (6^th Edition):

Hsu, F. (2017). ARTICULATION OF HUMAN ARTICULAR CARTILAGE INDUCES ANISOTROPIC STRUCTURAL DETERIORATION AND AGE-DEPENDENT CELLULAR RESPONSES. (Thesis). University of California – San Diego. Retrieved from http://www.escholarship.org/uc/item/7f51r8cd

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Hsu, Felix. “ARTICULATION OF HUMAN ARTICULAR CARTILAGE INDUCES ANISOTROPIC STRUCTURAL DETERIORATION AND AGE-DEPENDENT CELLULAR RESPONSES.” 2017. Thesis, University of California – San Diego. Accessed January 23, 2021. http://www.escholarship.org/uc/item/7f51r8cd.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Hsu, Felix. “ARTICULATION OF HUMAN ARTICULAR CARTILAGE INDUCES ANISOTROPIC STRUCTURAL DETERIORATION AND AGE-DEPENDENT CELLULAR RESPONSES.” 2017. Web. 23 Jan 2021.

Vancouver:

Hsu F. ARTICULATION OF HUMAN ARTICULAR CARTILAGE INDUCES ANISOTROPIC STRUCTURAL DETERIORATION AND AGE-DEPENDENT CELLULAR RESPONSES. [Internet] [Thesis]. University of California – San Diego; 2017. [cited 2021 Jan 23]. Available from: http://www.escholarship.org/uc/item/7f51r8cd.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Hsu F. ARTICULATION OF HUMAN ARTICULAR CARTILAGE INDUCES ANISOTROPIC STRUCTURAL DETERIORATION AND AGE-DEPENDENT CELLULAR RESPONSES. [Thesis]. University of California – San Diego; 2017. Available from: http://www.escholarship.org/uc/item/7f51r8cd

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of California – Berkeley

27. Ayala, Perla. Fabrication of Biocompatible Microstructures to Support Tissue Regeneration.

Degree: Bioengineering, 2011, University of California – Berkeley

URL: http://www.escholarship.org/uc/item/5jn6z78w

► Cardiac fibrosis is considered to be an independent risk factor in the outcome of congestive heart failure. Heart transplantation is the only treatment for patients… (more)

▼ Cardiac fibrosis is considered to be an independent risk factor in the outcome of congestive heart failure. Heart transplantation is the only treatment for patients who are at the end stage of this condition. Shortage of donor organs has created a need for therapeutic alternatives. This dissertation investigates new strategies for cardiac repair systems that could reduce pathological fibrosis and promote growth of myocytes at the site of injury. Design of successful engineered therapies for tissue regeneration relies on discerning how cell behavior can be modulated by chemical and physical cues. Recent studies have shown that external physical cues such as stiffness and geometry can affect cell morphology and function. In this work, the combinatorial effect of stiffness and micro-scale topographical cues on proliferation and gene expression is investigated in 2D and 3D. The 2D system consists of fibroblasts grown on "micropegged" polydimethylsiloxane (PDMS) substrates of different stiffness. The 3D system consists of fibroblasts encapsulated with poly(ethylene glycol) dimethacrylate (PEGDMA) "microrods" of different stiffness in matrigel to create a 3D culture with micro-scale cues of defined mechanical properties in the physiological range. Fibroblasts cultured on micropegged substrates have reduced collagen expression compared to fibroblasts cultured on flat substrates. Cells on stiffer micropegged substrates exhibit down regulation of important regulators of ECM synthesis but there is no down-regulation of these markers when cells are cultured on the softer micropegged substrates. Similarly, three-dimensional cultures with stiffer microrods show reduced fibroblast proliferation and down-regulation of collagen and other important regulators of ECM synthesis, but three dimensional cultures with soft microrods do not show significant difference on fibroblast proliferation and expression of some ECM regulators compared to cultures with no microrods. To determine whether microrods can influence myocardial repair and remodeling in vivo, adult female Sprague-Dawley rats undergo left anterior descending (LAD) artery occlusion for thirty minutes followed by reperfusion. Microrods suspended in PBS are injected into the left ventricle (LV) two days after myocardial infarction (MI). Five weeks after the injections echocardiography reveals an increase in ejection fraction (EF) in the microrod group compared to the PBS control. Histology analysis shows a trend on decreased amount of scar formation and increased wall thickness of the microrod treated group compared to the PBS control. Furthermore, it is shown that microrods can be utilized as growth factor delivery devices. Mechano growth factor (MGF) is expressed rapidly after tissue damage and prevents apoptosis in the myocardium; thus is considered a suitable therapeutic candidate for cardiac repair. Here, it is shown that microrods can be loaded with MGF and that the peptide can be eluted from the microrods for a period of days. Bioactivity of MGF is confirmed…

Subjects/Keywords: Biomedical engineering; Drug Delivery; Mechanobiology; Microfabrication; Tissue Engineering

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APA (6^th Edition):

Ayala, P. (2011). Fabrication of Biocompatible Microstructures to Support Tissue Regeneration. (Thesis). University of California – Berkeley. Retrieved from http://www.escholarship.org/uc/item/5jn6z78w

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Ayala, Perla. “Fabrication of Biocompatible Microstructures to Support Tissue Regeneration.” 2011. Thesis, University of California – Berkeley. Accessed January 23, 2021. http://www.escholarship.org/uc/item/5jn6z78w.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Ayala, Perla. “Fabrication of Biocompatible Microstructures to Support Tissue Regeneration.” 2011. Web. 23 Jan 2021.

Vancouver:

Ayala P. Fabrication of Biocompatible Microstructures to Support Tissue Regeneration. [Internet] [Thesis]. University of California – Berkeley; 2011. [cited 2021 Jan 23]. Available from: http://www.escholarship.org/uc/item/5jn6z78w.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Ayala P. Fabrication of Biocompatible Microstructures to Support Tissue Regeneration. [Thesis]. University of California – Berkeley; 2011. Available from: http://www.escholarship.org/uc/item/5jn6z78w

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Mississippi State University

28. Metzler, Scott Andrew. THE AORTIC VALVE ENDOTHELIAL CELL: A MULTI-SCALE STUDY OF STRAIN MECHANOBIOLOGY.

Degree: PhD, Agricultural and Biological Engineering, 2010, Mississippi State University

URL: http://sun.library.msstate.edu/ETD-db/theses/available/etd-04042010-131405/ ;

► The aortic valve (AV) functions in arguably the most demanding mechanical environment in the body. The AV experiences fluid shear stress, cyclic pressure and… (more)

▼ The aortic valve (AV) functions in arguably the most demanding mechanical environment in the body. The AV experiences fluid shear stress, cyclic pressure and mechanical strain in vivo. Recent evidence has shown the progression of degenerative aortic valve disease (AVD) to be an active cellular mediated process, altering the conception of the AV as a passive tissue. AVD has shown a strong correlation with altered hemodynamics and tissue mechanics. Aortic valve endothelial cells (AVECs) line the fibrosa (aortic facing) and ventricularis (left ventricle facing) surfaces of the valve. AVECs sense and respond to circulating stimuli in the blood stream while maintaining a non-thrombogenic layer. AVEC activation has been implicated in the initiation and progression of AVD, but the role of cyclic strain has yet to be elucidated. The hypothesis of this dissertation is that altered mechanical forces have a causal relationship with aortic valvular endothelial cell activation. To test this hypothesis 1) the role of in vitro cyclic strain in regulating expression of pro-inflammatory adhesion molecule was elucidated 2) cyclic strain-dependent activation of side-specific aortic valve endothelial cells was investigated 3) a novel stretch bioreactor was developed to dramatically increase the ability to correlate valvular endothelium response to physiologically relevant applied planar biaxial loads. The results from this study further the field of heart valve mechanobiology by correlating AVEC physiological and pathophysiological function to cellular and tissue level strain. Elucidating the AVEC response to an altered mechanical environment may result in novel clinical diagnostic and therapeutic approaches to the initiation and progression of degenerative AVD. Furthermore, a cardiovascular health outreach program, Bulldogs for Heart Health, has been designed and implemented to combat the startling rise in childhood obesity in the state of Mississippi. It is the hope that these results, novel methods, and outreach initiatives developed will significantly impact the study of the mechanobiology of the aortic valve endothelial cell and potential treatment and prevention of cardiovascular disease. Advisors/Committee Members: James N. Warnock (chair).

Subjects/Keywords: Aortic Valve Endothelial Mechanobiology

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APA (6^th Edition):

Metzler, S. A. (2010). THE AORTIC VALVE ENDOTHELIAL CELL: A MULTI-SCALE STUDY OF STRAIN MECHANOBIOLOGY. (Doctoral Dissertation). Mississippi State University. Retrieved from http://sun.library.msstate.edu/ETD-db/theses/available/etd-04042010-131405/ ;

Chicago Manual of Style (16^th Edition):

Metzler, Scott Andrew. “THE AORTIC VALVE ENDOTHELIAL CELL: A MULTI-SCALE STUDY OF STRAIN MECHANOBIOLOGY.” 2010. Doctoral Dissertation, Mississippi State University. Accessed January 23, 2021. http://sun.library.msstate.edu/ETD-db/theses/available/etd-04042010-131405/ ;.

MLA Handbook (7^th Edition):

Metzler, Scott Andrew. “THE AORTIC VALVE ENDOTHELIAL CELL: A MULTI-SCALE STUDY OF STRAIN MECHANOBIOLOGY.” 2010. Web. 23 Jan 2021.

Vancouver:

Metzler SA. THE AORTIC VALVE ENDOTHELIAL CELL: A MULTI-SCALE STUDY OF STRAIN MECHANOBIOLOGY. [Internet] [Doctoral dissertation]. Mississippi State University; 2010. [cited 2021 Jan 23]. Available from: http://sun.library.msstate.edu/ETD-db/theses/available/etd-04042010-131405/ ;.

Council of Science Editors:

Metzler SA. THE AORTIC VALVE ENDOTHELIAL CELL: A MULTI-SCALE STUDY OF STRAIN MECHANOBIOLOGY. [Doctoral Dissertation]. Mississippi State University; 2010. Available from: http://sun.library.msstate.edu/ETD-db/theses/available/etd-04042010-131405/ ;

University of Michigan

29. Sun, Yubing. Forcing Stem Cells to Behave: Dissecting the Mechanobiology of Human Pluripotent Stem Cells Using Microengineering Approaches.

Degree: PhD, Mechanical Engineering, 2015, University of Michigan

URL: http://hdl.handle.net/2027.42/113638

► Stem cells, especially human pluripotent stem cells (hPSCs), hold significant promise for modeling developmental and disease processes, drug and toxicology screening, and cell-based regenerative medicine.… (more)

▼ Stem cells, especially human pluripotent stem cells (hPSCs), hold significant promise for modeling developmental and disease processes, drug and toxicology screening, and cell-based regenerative medicine. Most hPSC studies have so far focused on identifying extrinsic soluble factors, intracellular signaling pathways, and transcriptional regulatory networks involved in regulating hPSC behaviors. This thesis focuses on the development and application of some novel synthetic micromechanical systems to understand the mechano-sensitive and -responsive properties of hPSCs and their functional regulation of self-renewal, directed differentiation, and survival of hPSCs. First, we have demonstrated that rigid PDMS micropost arrays (PMAs, Young’s modulus Eeff = 1MPa) support the maintenance of pluripotency of hPSCs. Blocking cytoskeleton contractility by blebbistatin and inhibiting E-cadherin functions by DECMA-1 antibody both impair mechanoresponsive self-renewal of hPSCs on rigid substrates. We have further achieved efficient neuroepithelial induction, caudalization, and motor neuron differentiation from hPSCs combing soft PMAs (Eeff < 5kPa) with dual Smad inhibition. The purity and yield of functional motor neurons derived from hPSCs within 23 days of culture using soft PMAs were improved four- and twelve-fold, respectively, compared to coverslips or rigid PMAs. Our mechanistic work has helped reveal for the first time that biomechanical cues, including intracellular contractile forces and cell shape, converge and reinforce signal integration of TGF-β, Wnt, Hippo/YAP, Rho GTPase, and the actomyosin cytoskeleton to regulate the neural plate specification. The last part of this thesis focuses on a novel acoustic tweezing cytometry (ATC) utilizing ultrasound pulses to actuate functionalized lipid-encapsulated microbubbles (MBs) targeted to cell surface integrin receptors to exert subcellular mechanical forces in the pN - nN range. ATC can robustly induce cell traction force changes through acoustic radiation forces and bubble cavitation induced shear stresses. Importantly, ATC stimulations increased the survival rate and cloning efficiency of hESCs by 3-fold, suggesting its potential application in large-scale expansion of hPSCs that is critical for future hPSC-based regenerative therapies and disease modeling. Advisors/Committee Members: Fu, Jianping (committee member), Krebsbach, Paul H. (committee member), O'Shea, Sue (committee member), Putnam, Andrew James (committee member), Liu, Allen Po-chih (committee member).

Subjects/Keywords: Mechanobiology; Pluripotent stem cells; substrate rigidity; YAP/TAZ; Mechanical Engineering; Engineering

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Sun, Y. (2015). Forcing Stem Cells to Behave: Dissecting the Mechanobiology of Human Pluripotent Stem Cells Using Microengineering Approaches. (Doctoral Dissertation). University of Michigan. Retrieved from http://hdl.handle.net/2027.42/113638

Chicago Manual of Style (16^th Edition):

Sun, Yubing. “Forcing Stem Cells to Behave: Dissecting the Mechanobiology of Human Pluripotent Stem Cells Using Microengineering Approaches.” 2015. Doctoral Dissertation, University of Michigan. Accessed January 23, 2021. http://hdl.handle.net/2027.42/113638.

MLA Handbook (7^th Edition):

Sun, Yubing. “Forcing Stem Cells to Behave: Dissecting the Mechanobiology of Human Pluripotent Stem Cells Using Microengineering Approaches.” 2015. Web. 23 Jan 2021.

Vancouver:

Sun Y. Forcing Stem Cells to Behave: Dissecting the Mechanobiology of Human Pluripotent Stem Cells Using Microengineering Approaches. [Internet] [Doctoral dissertation]. University of Michigan; 2015. [cited 2021 Jan 23]. Available from: http://hdl.handle.net/2027.42/113638.

Council of Science Editors:

Sun Y. Forcing Stem Cells to Behave: Dissecting the Mechanobiology of Human Pluripotent Stem Cells Using Microengineering Approaches. [Doctoral Dissertation]. University of Michigan; 2015. Available from: http://hdl.handle.net/2027.42/113638

Cornell University

30. Kelly, Natalie H. Transcriptomic analysis of cortical versus cancellous bone in response to mechanical loading and estrogen signaling.

Degree: PhD, Biomedical Engineering, 2017, Cornell University

URL: http://hdl.handle.net/1813/47742

► Osteoporosis is a skeletal disease characterized by low bone mass that often results in fracture. Mechanical loading of the skeleton is a promising approach to… (more)

▼ Osteoporosis is a skeletal disease characterized by low bone mass that often results in fracture. Mechanical loading of the skeleton is a promising approach to maintain or recover bone mass. Mouse models of in vivo loading differentially increase bone mass in cortical and cancellous sites. The molecular mechanisms behind this anabolic response to mechanical loading need to be determined and compared between cortical and cancellous bone. This knowledge could enhance the development of drug therapies to increase bone formation in osteoporotic patients. After developing a method to isolate high-quality RNA from marrow-free mouse cortical and cancellous bone, differences in gene transcription were determined at baseline and at two time points following mechanical loading of wild-type mice. Cortical and cancellous bone exhibited different transcriptional profiles at baseline and in response to mechanical loading. Enhanced Wnt signaling dominated the response in cortical bone at both time points, but in cancellous bone only at the early time point. In cancellous bone at the later time point, many muscle-related genes were downregulated. Decreased bioavailable estrogen levels are a major cause of bone loss in postmenopausal women. Estrogen signaling through estrogen receptor alpha (ER) has been found to be particularly important in regulating bone mass and the skeletal response to mechanical loading. We recently showed that mice lacking ER in osteoblasts and osteocytes (pOC-ERKO) had an increased adaptive response to mechanical loading, particularly in cancellous bone. The molecular mechanisms of functional adaptation to load in the context of decreased estrogen signaling are not fully elucidated, particularly in cortical versus cancellous sites. We examined transcription in cortical versus cancellous bone of tibiae from littermate control (LC) and pOC-ERKO mice. pOC-ERKO mice had a blunted transcriptional response to mechanical loading in cortical bone compared to littermate controls, but had an increased response in cancellous bone. This work demonstrates the importance of examining cortical and cancellous bone separately, and that next-generation sequencing is a powerful tool for discovering the complete transcriptional mechanisms responsible for mechanical loading-related bone anabolism. Advisors/Committee Members: van der Meulen, Marjolein (chair), Lammerding, Jan (committee member), Schimenti, John C. (committee member).

Subjects/Keywords: bone; mechanobiology; Biomedical engineering; RNA-sequencing; Biomechanics; Molecular biology; osteoporosis

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Kelly, N. H. (2017). Transcriptomic analysis of cortical versus cancellous bone in response to mechanical loading and estrogen signaling. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/47742

Chicago Manual of Style (16^th Edition):

Kelly, Natalie H. “Transcriptomic analysis of cortical versus cancellous bone in response to mechanical loading and estrogen signaling.” 2017. Doctoral Dissertation, Cornell University. Accessed January 23, 2021. http://hdl.handle.net/1813/47742.

MLA Handbook (7^th Edition):

Kelly, Natalie H. “Transcriptomic analysis of cortical versus cancellous bone in response to mechanical loading and estrogen signaling.” 2017. Web. 23 Jan 2021.

Vancouver:

Kelly NH. Transcriptomic analysis of cortical versus cancellous bone in response to mechanical loading and estrogen signaling. [Internet] [Doctoral dissertation]. Cornell University; 2017. [cited 2021 Jan 23]. Available from: http://hdl.handle.net/1813/47742.

Council of Science Editors:

Kelly NH. Transcriptomic analysis of cortical versus cancellous bone in response to mechanical loading and estrogen signaling. [Doctoral Dissertation]. Cornell University; 2017. Available from: http://hdl.handle.net/1813/47742

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