Probing Cellular Dynamic Mechanobiology Using Human Cardiomyocytes on a Stimuli-Responsive Nano-Topographic Substrate

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This grant will support a multidisciplinary research that will enable new approaches in dynamic cell mechanobiology and smart biomaterials. Traditionally, cell mechanobiology is studied using static culture systems. Though useful, these systems provide little knowledge as to how the cells respond to a dynamic changing microenvironment, such as in the body. This project aims to develop in vitro models and approaches that include time-dependent mechano-structural cues to cells. These physical cues are important to regulating of cellular morphology (shape), differentiation (what cells become), and function at each phase of tissue development or healing. The knowledge gained through this project will have a broad impact and various applications in the scientific fields related to developmental cell biology and cardiac pathophysiology. This project is also designed to integrate research, education, and diversity with an emphasis on strengthening research exposure and opportunities at different education levels. The educational component of this project aims to help raise the awareness and familiarity of high-school students and undergraduate students with interdisciplinary, emerging and socially compelling directions within biomedical engineering. The goal of the present research is to use an in vitro shape-memory polymer (SMP) platform to investigate how dynamic topographic structural cues affect cellular mechanobiology, with a particular emphasis on the focal adhesion dynamics of human cardiomyocytes. The combination of dynamic biomaterial substrates, hiPSC technology and genome editing will provide a great potential to establish new analytical tools and in vitro model systems for broadly studying time-dependent mechano-structural cues in dynamic cell mechanobiology. This dynamic platform will allow us to test our hypothesis that extracellular topographic changes will dictate the different dynamic responses of both periphery focal adhesions and sarcomere-linked costameres of cardiomyocytes, thereby reorganizing myofibril structures and controlling contractile functions. This project aims to study how dynamic structural cues would regulate periphery focal adhesions (Objective 1) and cardiac-specific sarcomere-linked costameres (Objective 2), and how mechanotransduction signaling pathways (FAK and YAP/TAZ) are involved in these cellular developmental processes (Objective 3).This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.