Undergraduate Honors Theses

Thesis Defended

Spring 2018

Document Type

Thesis

Type of Thesis

Departmental Honors

Department

Molecular, Cellular, & Developmental Biology

First Advisor

Leslie Leinwand

Second Advisor

Pamela Harvey

Third Advisor

Kristi Anseth

Abstract

Heart disease continues to be the leading cause of death in both men and women. It is accompanied with cellular- and organ- level remodeling that cannot be mimicked or recaptured by cells on standard culture platforms. Polyethylene glycol hydrogels bridge this gap by providing user-defined tunability for cell culture. A novel 3D cell culture system was developed to encapsulate neonatal rat ventricular cardiomyocytes (NRVMs) in a single plane, and cell health was assessed. In parallel, recombinant adenoviruses containing the mutations responsible for human hypertrophic cardiomyopathy (HCM) in the beta myosin gene (R403Q and R453C) were generated and used as a tool to study the acute effects of HCM. Expression and incorporation of the HCM mutant myosins in NRVMs were sufficient to cause a cellular disease phenotype; this work presents initial characterizations of the morphological, functional, and molecular differences. Cells cultured in 3D were viable and presented a heathly baseline for cardiomyocytes. This merits further studies to implement a 3D cell culture system to more accurately assess cellular disease characteristics. Disease progression can be deconvoluted if the characteristics are compared to a baseline that more appropriately resembles the healthy native tissue. This work and the possible future studies provide a foundation for better disease characterizations that can promote effective drug development.

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