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MECHANICS AND STRUCTURE OF THE CANCER GLYCOCALYX AND CELL SURFACE

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Abstract

The glycocalyx is a thick coat of proteins and carbohydrates on the outer surface of all eukaryotic cells. Overproduction of large, flexible or rod-like biopolymers, including hyaluronic acid and mucins in the glycocalyx strongly correlates with aggression of many cancer types. However, theoretical frameworks to predict the effects of these changes on cancer cell adhesion and other biophysical processes remain limited. A detailed modeling framework is proposed for the glycocalyx, incorporating important physical effects of biopolymer flexibility, excluded volume, counterion osmotic pressure, and coupled membrane deformations. Since the stiffness of mucin and hyaluronic biopolymers is proposed to depend on the extent of their decoration with side chains, two limiting cases for the structural elements of the glycocalyx are considered: stiff beams and flexible chains. Three applications are considered for the models: 1. Cancer cells frequently experience significant compressive stresses as they migrate through confined spaces between tissues or exist in highly packed tumors. The modeling frameworks were applied to characterize the mechanical response and structure of the glycocalyx and cell surface as a cancer cell is compressed externally. 2. Cancer cells use amoeboid motility to move at fast rates, often using bleb-like protrusions on the cell surface. Cells internally pressurize their cytosol to generate these blebs-like protrusions. Simulations of the models reveal the length and time scales at which the glycocalyx naturally deforms under a cytosolic pressure. 3. Cancer cells typically exhibit tube-like and bleb-like protrusions on the apical surface. Polymer brush theory explains the formation of these curved structures due to intermolecular interactions between flexible chains.

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204 pages

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Date Issued

2019-12

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Keywords

glycocalyx; mechanics; membrane; model; mucin; simulation

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Committee Chair

Paszek, Matthew J.
Koch, Donald L.

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Committee Member

Hui, Chung-Yuen

Degree Discipline

Chemical Engineering

Degree Name

Ph. D., Chemical Engineering

Degree Level

Doctor of Philosophy

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Government Document

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Attribution 4.0 International

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dissertation or thesis

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