DOI

https://doi.org/10.25772/SA9T-XZ61

Author ORCID Identifier

0000-0001-5219-2719

Defense Date

2022

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Biomedical Engineering

First Advisor

Daniel Conway

Abstract

The nucleus is the largest and stiffest organelle and is exposed to mechanical forces transmitted through the cytoskeleton from outside the cell, as well as from forces generation within the cell. In recent years, the nucleus has been proposed to act as a cellular mechanosensor, with changes to nuclear shape and architecture playing an important role in how the cell responds to physiological forces. Aberrant forms of the nuclear envelope protein lamin A/C, as well as epigenetic modifications to chromatin, has been shown to modify nuclear stiffness and viscosity, therefore effecting nuclear mechanics and mechanotransduction. Altered nuclear mechanics is associated with many human diseases, including heart disease, muscle dystrophy, progeria, and cancer. My PhD work explores how changes to the nuclear lamina protein lamin A/C, as well as changes to chromatin condensation, effects endothelial cell adaptation to fluid shear stress. In addition, I developed a novel lamin A/C intermolecular force sensor to better understand if the nuclear lamina experiences force and if so, identify the factors contributing to it.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

4-7-2022

Available for download on Friday, April 07, 2023

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