Date of Award

Spring 2013

Document Type

Thesis

Department

Mathematics, Engineering & Computer Science

First Advisor

Kelly Cline

Second Advisor

Philip Rose

Third Advisor

Stefanie Otto-Hitt

Abstract

In this paper, the effects of Hutchinson-Gilford progeria syndrome on endothelial cell’s mitochondrial response to shear stress will be discussed. I will also be addressing nuclear texture and differences in these same patient cells as compared to healthy cell lines. To accomplish this, I used cell culturing and fluorescent imaging techniques to gather images of cells to analyze the application of shear stress. I then used the Image Toolbox in Matlab to develop and implement a segmentation algorithm for these cells and ran analysis processes on them. Segmentation processes for the mitochondrial material and nuclear material were then developed. After segmentation, images were run though programs to perform Linear Optimal Transportation (LOT) analysis and some basic statistical tests. I found that after application of low shear stress for one hour, there was a spike in the amount of unhealthy mitochondria present. This returned to normal levels between one and six hours later. In the cells with the HGPS mutation, after the application of high shear stress, the mitochondria failed to recover and continued to show increases in the amount of unhealthy mitochondria. Differential clumping patterns of the unhealthy mitochondria were also observed in the HGPS cells as they gathered near the nucleus in larger clumps. Collectively, these results suggest that the endothelial cells of HGPS patients struggle to excrete the mitochondrial material.

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