Digitized Honors Theses (2002-2017)

Date of Award

5-2017

Document Type

Undergraduate Thesis

Degree Name

BS

Department

Biomedical Sciences

Faculty Mentor

Dhananjay Tambe, Ph.D.

Advisor(s)

Brad Swiger, Ph.D., Cindy Stanfield, Ph.D.

Abstract

Fifty million people worldwide suffer from chronic lung diseases with the only available treatment being lung transplantation; less than 1% benefit from this approach. An alternative is engineering bioartificial lungs which are generated by decellularizing donor lungs followed by autologous recellularization. Identifying properties of the microenvironrnent of the endothelial cell would shed light on why achieving a functional vasculature is a reigning problem in the field. The process of vessel recellularization requires each cell to go through processes of attachment, migration, division, and barrier formation. However, it is not clear how each of these processes is regulated in the heterogeneous mechanical microenvironrnent that exists along the pulmonary vasculature.

To enable quantitative assessment of how the local mechanical microenvironrnent regulates endothelial recellularization requires an appropriate analytical framework to quantitatively monitor cellular function, but none currently exists. The goal of this thesis is to explore the extent to which cellular function can be constructed around a measurable mechanical property of the cells. By tugging on its surrounding, which includes the extracellular matrix and its neighbor, an adherent cell would essentially be engaging in mechanical work. Key components of this mechanical work comprise of forces that the cell exerts on the substrate, the forces that the cell exerts on the neighbors, and deformation of the substrate. These properties can be obtained using the technique called Monolayer Stress Microscopy. Using advancing sheets of pulmonary endothelial cells, we have built the analytical framework and opened a window onto the relationship of the mechanical work with the processes including cellular attachment, migration and proliferation.

Comments

Copyright 2017 Shivani Ananthasekar ALL RIGHTS RESERVED

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