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  • Book
    Chelsey Savannah Simmons.
    Digital2013
    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.