Montana State University
Servid, Amy Eloise.
Characterization and embellishment of protein cages for nanomedical and nanomaterial applications.
Degree: PhD, College of Letters & Science, 2014, Montana State University
In nature, protein cages are found within the structures of viruses, heat shock proteins, and ferritins. They assemble from subunits into spherical oligomeric structures, which serve to encapsulate, protect, and/or deliver cargo. The fundamental understanding of protein cage structure is a key component in the design of novel nanomaterials that best exploit and expand upon the natural functions of protein cage architectures. By mimicking the re-occurring design strategies employed by natural systems, the protein cages produced during virus infection and/or stress responses can be modified to yield particles that fight disease and/or serve as the building blocks for materials design. In particular, the work described here highlights the design and characterization of protein cages in an effort to develop and uncover new strategies for immunization of the lung against a variety of pathogens. A combination of genetic and chemical engineering approaches is described here in order to better understand the structure of protein cage architectures and the relationship between the structure and in vivo function. This work describes the chemical cross-linking of large antigens and immunomodulatory molecules to the surface of a protein cages, and it shows that intensified and accelerated immune responses result from the display of antigens on a protein cage surface. Genetic incorporation of point mutations within the capsid structure provided unique attachment points for chemical functionalization. In addition, genetic modifications revealed information about the location of the C-terminus of the bacteriophage P22 capsid. The knowledge that this position was displayed on the capsid exterior prompted its use to promote inter-capsid interactions and target nanoparticles to melanoma cells. This research emphasizes that both the protein cage structural design and the local in vivo environment can influence the outcomes of protein cages when administered to the lung environment. It also lays the foundation for the logical design of biomaterials that offer enhanced protection against influenza and other respiratory diseases. Finally, regions of protein cages that are amendable to chemical and genetic modifications are described herein, and these have paved the way for the continued development of protein cage platforms for nanomedical and material applications.
Advisors/Committee Members: Chairperson, Graduate Committee: Trevor Douglas (advisor), Laura E. Richert, Ann L. Harmsen, Agnieszka Rynda-Apple, Soo Han, James A. Wiley, Trevor Douglas and Allen G. Harmsen were co-authors of the article, 'A virus-like particle vaccine platform elicits heightened and hastened local lung mucosal antibody production after a single dose' in the journal 'Vaccine' which is contained within this thesis. (other), Paul Jordan, Alison O'Neil, Peter Prevelige and Trevor Douglas were co-authors of the article, 'Location of the bacteriophage P22 coat protein C-terminus provides opportunities for the design of capsid-based materials' in the journal 'Biomacromolecules' which is contained within this thesis. (other).
Subjects/Keywords: Protein engineering.; Nanomedicine.; Lungs.; Immunology.
to Zotero / EndNote / Reference
APA (6th Edition):
Servid, A. E. (2014). Characterization and embellishment of protein cages for nanomedical and nanomaterial applications. (Doctoral Dissertation). Montana State University. Retrieved from https://scholarworks.montana.edu/xmlui/handle/1/9137
Chicago Manual of Style (16th Edition):
Servid, Amy Eloise. “Characterization and embellishment of protein cages for nanomedical and nanomaterial applications.” 2014. Doctoral Dissertation, Montana State University. Accessed July 07, 2020.
MLA Handbook (7th Edition):
Servid, Amy Eloise. “Characterization and embellishment of protein cages for nanomedical and nanomaterial applications.” 2014. Web. 07 Jul 2020.
Servid AE. Characterization and embellishment of protein cages for nanomedical and nanomaterial applications. [Internet] [Doctoral dissertation]. Montana State University; 2014. [cited 2020 Jul 07].
Available from: https://scholarworks.montana.edu/xmlui/handle/1/9137.
Council of Science Editors:
Servid AE. Characterization and embellishment of protein cages for nanomedical and nanomaterial applications. [Doctoral Dissertation]. Montana State University; 2014. Available from: https://scholarworks.montana.edu/xmlui/handle/1/9137