CAREER: Integrated Micro-Electro-Mechanical-System for Cellular Mechanotransduction Studies

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Cellular mechanotransduction, the mechanism by which cells convert a mechanical stimulus into biochemical activities, widely affects a broad array of physiological processes. The mechanical stimulus is perceived and processed by cells and tissues through a highly complicated process regulated by a large number of biomolecules, subcellular components and extracellular structures, which eventually leads to appropriate biochemical responses. Understanding mechanotransduction requires engineering devices that can provide in situ assessment, in a controlled environment, of the cell response to systematically variable external mechanical stimuli mimicking the combinatorial mechanical loads (compressive/tensile) found in vivo.In this CAREER project, fully automated cellular mechanotransduction analysis will be streamlined through the development of an integrated micro-electro-mechanical-system (MEMS). The device will simplify the analysis of cells and tissues by minimizing external influence and will provide direct correlation between an applied mechanical stimulus and the activity of critical mechanosensitive biomolecules. The device will enable application of independently controllable combinational mechanical signals with preferred magnitudes, frequency, and duration to cells on loading sites. The use of a microfluidic network will allow parallel actuation of a large number of cells, and in situ intercellular and intracellular analysis. Use of the device will be simplified by developing instrumental and software interfaces. The efficacy of the device will be evaluated using skeletal myoblasts C2C12. By enabling quantitative study mechanotrandcution pathways, the device will help in the study of mechanisms that govern physiologic and pathologic conditions of mechanosensitive cells.The CAREER project will integrate the PI's research, education and outreach activities. The research outcome will be incorporated into courses and laboratory modules, benefitting students from both engineering fields and biology. The research discoveries will be disseminated through archival journals and conference presentations. Meanwhile, the research will provide a vehicle to deliver math, technological and engineering science in an exciting, practical, and interactive environment to minority and women students through the institutional Engineers in Motion program, and to K-12 students through collaboration with a local high school.The project outcome will also be available at the lab website http://www.bme.ohio-state.edu/yizhao/.