Date of Award
Doctor of Philosophy (PhD)
Dr. Bruce Z. Gao, Committee Chair
Dr. Thomas K. Borg
Dr. Delphine Dean
Dr. Hai Yao
Cardiac hypertrophy is the enlargement of individual cardiac muscle cell (cardiomyocyte) in both size and mass, which is achieved by addition of sarcomeres, the basic contractile unit. Cardiomyocytes elongate by adding sarcomeres in series and thicken by adding sarcomeres in parallel. Though it is generally accepted that sarcomeric addition can be initiated by increased mechanical loading, the sarcomeric addition process under various mechanical overloads on molecular level remains largely unknown. Previous research on sarcomeric addition largely rely on animal models of induced cardiac hypertrophy; those experiments provide little direct evidence for sarcomeric addition process as a response to increased mechanical loading, aside from the start and end point conditions. Studies showing the dynamic addition process of sarcomeric addition are rare, due to lack of in vivo-like cardiomyocyte culture models for mechanical assays and limited choice of live imaging techniques. In this project, a 3D cardiomyocyte culture model that recapitulates the in vivo-like mechanical loading environment, was established in vitro on a 2D PDMS substrate. With this culture model, we, for the first time, revealed the dynamic sarcomeric addition process at intercalated discs and Z discs with custom-built passive pulse splitter-based TPEF-SHG microscope, which confirmed the long-standing hypothesis of sarcomeric addition at intercalated discs and Z discs. These findings may advance the comprehension of cardiomyocyte remodeling process on sarcomeric level during development of cardiac hypertrophy.
Wang, Zhonghai, "Real-time Observation of Dynamic Sarcomeric Addition in an In Vivo-like Cardiomyocyte Culture Model" (2017). All Dissertations. 1978.