DOI
https://doi.org/10.25772/GQW8-2S20
Defense Date
2023
Document Type
Dissertation
Degree Name
Doctor of Philosophy
Department
Biomedical Engineering
First Advisor
Christopher A. Lemmon
Abstract
Despite decades of investigations into fibronectin (FN) fibrillogenesis, fibril mechanics remain unclear. One of the most important roles for FN fibrils is in the arena of cellular mechanotransduction. Numerous studies have demonstrated that cells sense and respond to the mechanical properties of their surroundings; since FN fibrils are a major constituent of the ECM that links cells to their surroundings, mechanotransduction cannot be fully understood without understanding the mechanical properties of FN fibrils. In this proposal, a novel biomechanical assay is developed to probe isolated FN fibrils and quantify their response to specific loading conditions. This will be accomplished by using optical tweezers (OT) to strain cell-assembled FN fibrils suspended between micropillar arrays (MPA) in a unique technique described here as Antibody-Mediated Optical Tweezing (AMOT). At the conclusion of the project, constitutive modeling of the elastic and viscoelastic parameters FN fibrils will be elucidated. These foundational findings will help clarify the role of FN in mechanotransduction and ECM mechanics in different tissues. The proposed research will shift current approaches of mechanobiology to incorporate cell-derived, cell-free experiments to investigate fundamental characteristics of native ECM components and their responsibilities in mechanotransduction.
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
8-9-2023