The Biophysical Role of the Cellular Glycocalyx: Engineering Glycoproteins to Control Cell-Surface Properties

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Abstract
The glycocalyx is the sugary coating on the surface of essentially all mammalian cells. Despite being a major class of biomolecules, research into carbohydrates has lagged behind other classes of biomolecules such as nucleic acids and proteins. The constituent parts of the glycocalyx are not encoded in our genome, but rather dynamically regulated by protein expression rates, post-translational modification rates, and metabolic flux. Therefore, we can view the glycocalyx as a complex and dynamic biomaterial on the surface of cells; however, research into the impact of the glycocalyx as a biomaterial is lacking. Coating the cellular surface, the glycocalyx is uniquely positioned to impact many different cell-surface properties including regulation of cell-cell and cell-extracellular matrix interactions, cell-surface features, and cellular migration. Throughout this work, we approach the glycocalyx as a biomaterial coating on the surface of cells with the goal of appreciating the physical properties and implications of the material. We first use an engineering approach to develop a new set of genetically encoded mucin biopolymers to facilitate in studying the cancer glycocalyx. We then apply our expertise in synthetic biology approaches and mucin biopolymer expression to produce some of the first ever recombinant mucins for therapeutic applications. Taking advantage of the anti-adhesive properties of mucin, we apply mucin expression as an innovative technology for reduced aggregation of cells grown in suspension in bioreactors. With our unique viewpoint of the glycocalyx from a physical perspective, we apply polymer brush theory to develop a model for membrane bending driven by glyco-biopolymers. Finally, we investigate what role the anti-adhesive glycocalyx may play in regulating cellular migration both in vitro and in vivo. Together, these projects utilize engineered glycoproteins to elucidate new functions for the mammalian glycocalyx in various avenues of cellular behavior and inform future research into the physical role of the glycocalyx at the cell surface.
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2019-08-30
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migration; Biophysics; adhesion; bioprocess; membrane morphology; mucin; Biomedical engineering; Chemical engineering; synthetic biology
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Paszek, Matthew J.
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Stroock, Abraham Duncan
Lammerding, Jan
Degree Discipline
Chemical Engineering
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Ph.D., Chemical Engineering
Degree Level
Doctor of Philosophy
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Government Document
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dissertation or thesis
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