Date of Award

5-2016

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Legacy Department

Economics

Committee Member

Dr. Delphine Dean, Committee Chair

Committee Member

Dr. Agneta Simionescu

Committee Member

Dr. Jeremy Mercuri

Committee Member

Dr. Bruce Gao

Abstract

The goal of this dissertation is to better understand cellular mechanics across length scales for the development of computational models of tissue behavior. To this end, we had two major approaches, multidimensional and multimodal. Firstly, to use a model that better mimics in vivo like cellular environment, microtissue (spheroid) cell culture system was used to study cell mechanics. Secondly, a novel technique was designed to study single cell mechanics in multiple dimensions. Cell mechanical properties are directly related to the composition and organization of the cytoskeleton, which is physically coupled to neighboring cells through adherens junctions and to extracellular matrix through focal adhesion complexes. As such, we hypothesize that the variations in cellular interactions affects cell mechanics. To test our hypothesis, cardiomyocytes and vascular smooth muscle microtissues were cultured under several conditions that limited the cell-cell and cell-matrix interactions. Cell interactions facilitated by integrin β1, connexin 43, and N-cadherin was inhibited and their effect on cell stiffness was characterized by atomic force microscopy (AFM). Currently, there does not exist a single technique that can measure mechanics of a single cell in two different dimensions. To address this gap, we designed a novel set up that combines two different single cell mechanics measurement techniques, AFM and carbon fiber. This combination allows for characterization of mechanical properties of single cells in multiple dimensions. The results of these studies provide insights from a basic science perspective. The results provide information regarding cell mechanics in multiple dimensions at both single cell as well microtissue level. The ultimate fulfillment of this work would be its incorporation into a multiscale model, leading to the ability to tie macro- scale behaviors to nano- scale phenomenon. Such models may help to better understand tissue behavior and further our understanding of the etiology of many diseases.

Share

COinS