Undergraduate Honors Theses

Thesis Defended

Spring 2015

Document Type

Thesis

Type of Thesis

Departmental Honors

Department

Molecular, Cellular, & Developmental Biology

First Advisor

Dr. Leslie Leinwand

Second Advisor

Dr. Jennifer Martin

Third Advisor

Dr. Eric Chwang

Fourth Advisor

Dr. William Wan

Abstract

It’s been shown that the microenvironments to which cells are exposed influence their shape and gene expression. Traditionally, because of the difficulty of studying cells in the body, cells are removed from the organism and are cultured on glass or plastic surfaces such as tissue culture polystyrene (TCPS). One limitation of studying cells on TCPS is its non-physiologic stiffness. In fact, TCPS is 106-fold stiffer than a healthy heart. In the interest of studying cardiac disease in a more physiologic context, we used a photodegradable hydrogel cell culture platform that can be manipulated with light to more closely represent the environments that neonatal rat ventricular myocytes (NRVMs) are exposed to in vivo. Frequently, as cardiac disease progresses, the cardiac muscle becomes stiffer and the cells become less organized. Our research used UV light to create patterns in these hydrogels in order to better mimic diseased and healthy states of a heart and thus encourage cells to maintain their native phenotypes. The hydrogels that were created influenced both the degree of cell alignment and expression levels of genes known to be sensors of health and disease (MHY6, MYH7, ANF, COL1A1, ACTA1, CCN2, ATP2A2, CACNA1C, and MMP2). Over all, alignment indices and expression levels of many of the genes offer strong evidence in support of the claim that a PEG hydrogel system is a healthier environment for NRVMs than TCPS is. In the future, these gels may be used as a more physiological alternative for culturing NRVMs for cardiac disease research.

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