Date of Award

12-2021

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Bioengineering

Committee Chair/Advisor

Dr. Bruce Z. Gao

Committee Member

Dr. Brian Booth

Committee Member

Dr. Delphine Dean

Committee Member

Dr. Dan Simionescu

Abstract

Cardiac hypertrophy is the response of the heart to increased mechanical stress exerted on the heart. In a hypertrophic heart, the muscles elongate or/and thicken with cardiomyocytes growing sizes. It is assumed that cardiomyocytes elongate by adding sarcomeres in series; the cardiomyocytes thicken with the addition of sarcomeres in the parallel position.

In this study, a tissue-like culture model was achieved with step-like ICDs. Uniaxial static stretch has been applied to our unique culture model for studying mechanical-load-induced cardiac hypertrophy. Hypertrophic responses of these cardiomyocytes have been confirmed on transcriptional and translational levels in our tissue-like model. The two-photon excitation fluorescence (TPEF)/second harmonic generation (SHG) imaging system is a powerful tool for studying the dynamic process of sarcomeric addition in a tissue-like culture. In this study, we determined the dynamic process of sarcomeric addition triggered by mechanical stimulations. For the first time, various modes of dynamic sarcomeric addition were observed at step-like ICDs. To conclude: Z discs and ICDs are the places where sarcomeric addition occurs. The sarcomeric addition order is 1) Z discs widen or form clusters at the sarcomere addition location; 2) myosins insert in the middle of the widened Z discs as myosin nucleus; 3) myosins grow into the typical length; 4) the widen Z disc split up and gradually thin back.

Available for download on Monday, November 28, 2022

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