Author ORCID Identifier

https://orcid.org/0000-0003-1401-6882

Defense Date

2022

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Biomedical Engineering

First Advisor

Christopher Lemmon

Abstract

It has been well established that there is a link between substrate stiffness and cellular activities such as proliferation, migration, and differentiation. Less characterized is the link between the time-dependent viscosity of a substrate with those cellular activities. To explore this, PDMS substrates were created with predictably tunable stiffness and viscosity parameters. A simulated model was also developed in parallel to explore the potential effects of viscosity in a computationally predictive way. It was found that the inclusion of viscosity caused a major paradigm shift to a non-zero substrate equilibrium that was sensitive to increases in the substrate stiffness. Finally, cell viability, size, and extracellular matrix assembly experiments were performed using a variety of the tunable PDMS substrates and it was found that generally the way cells responded to the changes in viscosity was linked to the stiffness, with parameters such as fibronectin area per cell showing that on stiff, viscous substrates the total amount of fibronectin was similar to soft, elastic and soft, viscous substrates. It was also found that viscosity can either enhance or inhibit the effects of chemical inhibitors such as FUD. It was found that high stiffness, high viscosity substrates maintained their cell size when exposed to the Fn inhibitor FUD while every other case showed a decrease in the cell area. This example highlights a new, novel field of cellular mechanobiology. Future work investigating the mechanisms behind this phenomenon may lead to more novel cellular mechanobiology based treatments for regenerative medicine applications.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

8-11-2022

Available for download on Friday, August 11, 2023

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