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

细胞机械转导是指细胞将机械刺激转化为生物化学活动的机制，它广泛地影响着一系列的生理过程。机械刺激被细胞和组织感知和加工，是一个高度复杂的过程，受到大量生物分子、亚细胞成分和细胞外结构的调控，最终导致相应的生化反应。理解机械转导需要工程设备，这些设备可以在受控环境中对细胞对系统可变的外部机械刺激的反应进行原位评估，模拟体内发现的组合机械负荷（压缩/拉伸）。在这个CAREER项目中，全自动细胞机械转导分析将通过集成微机电系统（MEMS）的开发而简化。该设备将通过最小化外部影响来简化细胞和组织的分析，并将提供应用机械刺激与关键机械敏感生物分子活性之间的直接关联。该装置将能够将具有首选幅度、频率和持续时间的独立可控组合机械信号应用于加载现场的单元。微流控网络的使用将允许并行驱动大量细胞，并在原位细胞间和细胞内分析。通过开发仪器和软件接口，将简化设备的使用。将使用成骨骼肌细胞C2C12来评估该装置的疗效。通过定量研究机械传导途径，该装置将有助于研究机械敏感细胞的生理和病理状况。职业发展项目将综合PI的研究、教育和外联活动。研究成果将纳入课程和实验模块，使工程和生物领域的学生受益。研究发现将通过档案期刊和会议报告传播。与此同时，这项研究将提供一种工具，通过“运动中的工程师”项目，在一个令人兴奋的、实用的、互动的环境中，向少数族裔和女性学生传授数学、技术和工程科学，并通过与当地一所高中的合作，向K-12学生传授科学。项目成果也将在实验室网站http://www.bme.ohio-state.edu/yizhao/上公布。

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/.