Mechanical stimulation and non-destructive functional assessment of cardiovascular cells in vitro

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Abstract/Contents

Abstract
The heart is a complex integrated system that leverages mechanoelectrical signals to synchronize cardiomyocyte contraction and push blood throughout the body. Due to the heart's limited regenerative capacity and the wide variety of cardiovascular pathologies, heart disease is often studied in vitro. However, it is difficult to accurately replicate the cardiac environment outside of the body. In this dissertation, I describe an integrated strain array for cell culture that mimics the mechanical movement of the heart and enables high-throughput mechanotransduction studies. Along with mechanical strain, substrate stiffness is an important mechanical stimulus. The heart and vasculature, along with other organs, remodel in both development and disease, changing their mechanical properties. I successfully implement a method that can simultaneously tune both substrate stiffness and mechanical strain in normal and pathological ranges. Polyacrylamide gels, attached to stretchable silicone platforms by interpenetrating networks, can be stretched up to 50% without delaminating. To fully harness the potential of studying heart disease in vitro, better techniques for studying heart cell contractions are required in addition to biomimetic dynamic culture. In this dissertation, I also describe two successful new approaches to quantifying cardiomyocyte contractility using simple phase contrast videos: one for single cells plated on soft gels and one for cell monolayers attached to glass or plastic. Together, these innovations provide a suite of tools to stimulate and assess cardiovascular cells and advance our collective knowledge of cardiovascular health and disease.

Description

Type of resource text
Form electronic; electronic resource; remote
Extent 1 online resource.
Publication date 2013
Issuance monographic
Language English

Creators/Contributors

Associated with Simmons, Chelsey Savannah
Associated with Stanford University, Department of Mechanical Engineering.
Primary advisor Pruitt, Beth
Thesis advisor Pruitt, Beth
Thesis advisor Kenny, Thomas William
Thesis advisor Nelson, W. J. (W. James)
Advisor Kenny, Thomas William
Advisor Nelson, W. J. (W. James)

Subjects

Genre Theses

Bibliographic information

Statement of responsibility Chelsey Savannah Simmons.
Note Submitted to the Department of Mechanical Engineering.
Thesis Thesis (Ph.D.)--Stanford University, 2013.
Location electronic resource

Access conditions

Copyright
© 2013 by Chelsey Savannah Simmons
License
This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).

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