Defense Date

2018

Document Type

Thesis

Degree Name

Master of Science

Department

Biomedical Engineering

First Advisor

Daniel E. Conway

Abstract

Cells regularly take on various types of force in the body. They have structures that are able to mediate, transfer and respond to the forces. A mutation in force regulating proteins such as lamin in the nucleus or the KASH domain which connects the nucleus to the cytoskeleton of the cell can cause catastrophic events to occur. The aims of this study were to better understand the response of the nucleus when structural proteins are mutated or are not present while under force. Progeria, a rare disease where an additional farnesyl group is attached to lamin was used in this study. Different types of forces were used to represent similar conditions in the body. Confinement of endothelial cell width showed an increase of surface defects. When restricting proteins such as actin was removed the nucleus appeared to rupture. This was shown to occur at a higher rate in the progeria groups. Endothelial cells under shear force showed high amount of nuclear rupture in progeria expressing group. prolonged exposure showed more rupture which eventually cased cell death and cells to come off the surface. Progeria expressing smooth muscle cells under cyclic stretch also showed similar results as endothelial cells. The amount and rate of deformation of the nucleus when the cytoskeleton is connected and not was looked at. When the connected the rate of deformation was higher. The high rate of nuclear defects and rupture while under force in progeria expressing cells shows that the nuclei have different structural properties and are weaker. It’s also been shown that the LINC complex contributes to nuclear deformation when stretching.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

5-11-2018

Available for download on Saturday, May 11, 2019

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