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