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You searched for subject:(Cellular adhesion dynamics). Showing records 1 – 3 of 3 total matches.

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Boston University

1. Vargas Arango, Diego Alejandro. Contributions of cluster shape and intercellular adhesion to epithelial discohesion and emergent dynamics in collective migration.

Degree: PhD, Biomedical Engineering, 2016, Boston University

As a physical system, a cell interacts with its environment through physical and chemical processes. The cell can change these interactions through modification of its environment or its own composition. This dissertation presents the overarching hypothesis that both biochemical regulation of intercellular adhesion and physical interaction between cells are required to account for the emergence of cluster migration and collective dynamics observed in epithelial cells. Collective migration is defined as the displacement of a group of cells with transient or permanent cell-cell contacts. One mode, cluster migration, plays an important role during embryonic development and in cancer metastasis. Despite its importance, collective migration is a slow process and hard to visualize, and therefore it has not been thoroughly studied in three dimensions (3D). Based on known information about cluster migration from 2D studies of epithelial sheets and 3D single cell migration, this dissertation presents theoretical and experimental techniques to assess the independent contribution of physical and biochemical factors to 3D cluster migration. It first develops two computational models that explore the interaction between cells and the ECM and epithelial discohesion. These discrete mechanistic models reveal the need to account for intracellular regulation of adherens junctions in space and time within a cluster. Consequently, a differential algebraic model is developed that accounts for cross-reactivity of three pathways in a regulatory biochemical network: Wnt/β-catenin signaling, protein N-glycosylation, and E-cadherin adhesion. The model is tested by matching predictions to Wnt/β-catenin inhibition in MDCK cells. The model is then incorporated into a self-propelled particle (SPP) model, creating the first SPP model for study of adhesive mammalian cellular systems. MDCK cell clusters with fluorescent nuclei are grown, seeded, and tracked in 3D collagen gels using confocal microscopy. They provide data on individual cell dynamics within clusters. Borrowed from the field of complex systems, normalized velocity is used to quantify the order of both in vitro and simulated clusters. An analysis of sensitivity of cluster dynamics on factors describing physical and biochemical processes provides new quantitative insights into mechanisms underlying collective cell migration and explains temporal and spatial heterogeneity of cluster behavior.

Subjects/Keywords: Biomedical engineering; Biological modeling; Cell-cell adhesion; Cellular pathway; Collective migration; Metastasis; Nonlinear dynamics

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APA (6th Edition):

Vargas Arango, D. A. (2016). Contributions of cluster shape and intercellular adhesion to epithelial discohesion and emergent dynamics in collective migration. (Doctoral Dissertation). Boston University. Retrieved from http://hdl.handle.net/2144/14623

Chicago Manual of Style (16th Edition):

Vargas Arango, Diego Alejandro. “Contributions of cluster shape and intercellular adhesion to epithelial discohesion and emergent dynamics in collective migration.” 2016. Doctoral Dissertation, Boston University. Accessed August 10, 2020. http://hdl.handle.net/2144/14623.

MLA Handbook (7th Edition):

Vargas Arango, Diego Alejandro. “Contributions of cluster shape and intercellular adhesion to epithelial discohesion and emergent dynamics in collective migration.” 2016. Web. 10 Aug 2020.

Vancouver:

Vargas Arango DA. Contributions of cluster shape and intercellular adhesion to epithelial discohesion and emergent dynamics in collective migration. [Internet] [Doctoral dissertation]. Boston University; 2016. [cited 2020 Aug 10]. Available from: http://hdl.handle.net/2144/14623.

Council of Science Editors:

Vargas Arango DA. Contributions of cluster shape and intercellular adhesion to epithelial discohesion and emergent dynamics in collective migration. [Doctoral Dissertation]. Boston University; 2016. Available from: http://hdl.handle.net/2144/14623

2. Behr, Julie Marie. Multiscale Modeling of Cancer Cell Adhesion.

Degree: MS, Bioengineering, 2013, Penn State University

The work described in this thesis is one component of a larger-scaled group effort to create a simulation tool that can represent populations of cell types and substrates moving through a flow field and find the probability of aggregates of cells forming. Specifically, this project seeks to define the biochemistry between a circulating melanoma cell and an adherent neutrophil (PMN, in particular), and how the forces acting on the melanoma cell from the surrounding fluid, ability of the cell to deform, and adhesion to the PMN affect the mechanisms leading to melanoma cell metastasis. Metastasis is the process by which a cancerous cell leaves a primary tumor site somewhere in the body, travels through the vasculature, and eventually leaves the vasculature to start a secondary tumor at a distant site. To attempt to define the factors enabling a melanoma cell to metastasize, this biochemistry simulation tool will define the adhesion molecules present on the melanoma and PMN cell surfaces, and calculate their interactions as the melanoma cell moves past the PMN in a flow field. Based on the proximity of the two cells, it may be possible for molecular bonds to form, which apply an adhesive force to the tumor cell. Within the structure of a computational fluid dynamics solver, information is available to define many locations across each cell surface, where individual molecules can be simulated. Within this work, a model will be defined for determining the biochemical rates of reactions between individual molecules, based on their local individual characteristics. All models and computational routines will be made robust enough to allow for future modifications and additional considerations to be incorporated into the model, including an unlimited number of adhesion molecule types to considered, and the ability to redefine the values of parameters to represent different cell types, rather than specifically melanoma cell and neutrophils. For the sake of this model, it is assumed that the neutrophil has already adhered to the endothelial surface, and therefore selectins (which aid in the initial interaction between white blood cells and the endothelium) were not simulated. The melanoma cell in the model expresses ICAM-1 molecules on its surface, and the PMN expresses the B-2 integrins LFA-1 and Mac-1. The PMN is fully rigid, but the melanoma cell is able to move with six degrees of freedom. Computational fluid dynamics is performed using the in-house developed software NPHASE, in which routines describing the biochemistry have been embedded. The biochemistry routines contain both adhesion, representing the ability of molecules to bond and adhere the cells to each other, and repulsion, which represents microvilli, which are not explicitly modeled, pushing the cells apart. Although this project considered melanoma cells and white blood cells, the routines developed in this work can be applied to any cell type of interest, by redefining values of the input parameters. These routines make it possible to run computational fluid…

Subjects/Keywords: cellular adhesion; computational fluid dynamics; binding affinity; melanoma; cancer cells

…representative of selectin interactions as well. 1.3 Adhesion Models Adhesion molecules on cellular… …critical adhesion distance λ. 1.4 Computational Fluid Dynamics (CFD) Modeling… …approaches 0 or equilibrium adhesion distance. (a) Bond formation between the cells when… …This simplified version of a mesh was used to run the Adhesion model through MATLAB without… …4.3 MATLAB model of Adhesion routine, affinity values plotted against separation distance… 

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

APA (6th Edition):

Behr, J. M. (2013). Multiscale Modeling of Cancer Cell Adhesion. (Masters Thesis). Penn State University. Retrieved from https://etda.libraries.psu.edu/catalog/18074

Chicago Manual of Style (16th Edition):

Behr, Julie Marie. “Multiscale Modeling of Cancer Cell Adhesion.” 2013. Masters Thesis, Penn State University. Accessed August 10, 2020. https://etda.libraries.psu.edu/catalog/18074.

MLA Handbook (7th Edition):

Behr, Julie Marie. “Multiscale Modeling of Cancer Cell Adhesion.” 2013. Web. 10 Aug 2020.

Vancouver:

Behr JM. Multiscale Modeling of Cancer Cell Adhesion. [Internet] [Masters thesis]. Penn State University; 2013. [cited 2020 Aug 10]. Available from: https://etda.libraries.psu.edu/catalog/18074.

Council of Science Editors:

Behr JM. Multiscale Modeling of Cancer Cell Adhesion. [Masters Thesis]. Penn State University; 2013. Available from: https://etda.libraries.psu.edu/catalog/18074


University of Minnesota

3. Chan, Clarence Elvin. Cellular adhesion dynamics: investigation of molecular clutch attachment and force transmission.

Degree: PhD, Biomedical Engineering, 2008, University of Minnesota

As the major structural element of the cell, the cytoskeleton plays a vital role in response and transmission of forces in both extracellular and intracellular environments. For instance, in cell motility, the cell utilizes a host of proteins to physically link F-actin to the extracellular substrate, allowing the cell to exert traction forces as well as probe the mechanics of its local environment. During mitosis, the cell constructs a mitotic spindle, using microtubules and kinetochores to exert forces that segregate sister chromatids. Ultimately, understanding how cells build these robust molecular machines for unique tasks could one day lead to therapeutics that treat disease causing dysfunctions in these vital cellular processes. In order to explore how molecular clutches work in concert with the cytoskeleton to exert forces and maintain attachment under load, we developed a mechano-chemical cellular adhesion dynamics framework to simulate these processes. In the case of cellular motility, we find that a "motor-clutch" mechanism exhibits substrate-stiffness sensitive dynamics. On soft substrates, motor-clutch motility exhibits "load-and-fail" dynamics that lead to higher rates of retrograde flow and lower traction force transmission compared to stiff substrates. We confirm these predictions experimentally using embryonic chick forebrain neurons (ECFNs) plated on compliant polyacrylamide gels (PAGs) demonstrating that a motor clutch system could be the basis of cellular mechanosensing. We also use cellular adhesion dynamics to explore kinetochore-microtubule attachment during mitosis to identify what properties might be important in maintaining attachment during mitosis. We show that molecular clutch microtubule-lattice diffusion is important for relieving clutch stresses, prolonging bond life-times and minimizing detachment forces. Furthermore, molecular clutches that preferentially associate with interdimer interfaces, rather than with intradimer interfaces, promote robust kinetochore attachment by preventing the more distal, attachment-promoting linkers from becoming nonproductive. These findings help further our understanding of the mechanochemical basis of kinetochore attachment and mitosis, a process essential throughout development.

Subjects/Keywords: Cellular adhesion dynamics; Focal adhesions; Integrins; Kinetochores; Molecular clutch; Biomedical Engineering

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

APA (6th Edition):

Chan, C. E. (2008). Cellular adhesion dynamics: investigation of molecular clutch attachment and force transmission. (Doctoral Dissertation). University of Minnesota. Retrieved from http://purl.umn.edu/58039

Chicago Manual of Style (16th Edition):

Chan, Clarence Elvin. “Cellular adhesion dynamics: investigation of molecular clutch attachment and force transmission.” 2008. Doctoral Dissertation, University of Minnesota. Accessed August 10, 2020. http://purl.umn.edu/58039.

MLA Handbook (7th Edition):

Chan, Clarence Elvin. “Cellular adhesion dynamics: investigation of molecular clutch attachment and force transmission.” 2008. Web. 10 Aug 2020.

Vancouver:

Chan CE. Cellular adhesion dynamics: investigation of molecular clutch attachment and force transmission. [Internet] [Doctoral dissertation]. University of Minnesota; 2008. [cited 2020 Aug 10]. Available from: http://purl.umn.edu/58039.

Council of Science Editors:

Chan CE. Cellular adhesion dynamics: investigation of molecular clutch attachment and force transmission. [Doctoral Dissertation]. University of Minnesota; 2008. Available from: http://purl.umn.edu/58039

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