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

细胞机械转导是细胞将机械刺激转化为生化活动的机制，广泛影响着一系列的生理过程。机械刺激是细胞和组织通过一个高度复杂的过程来感知和处理的，这个过程受到大量生物分子、亚细胞成分和细胞外结构的调控，最终导致适当的生化反应。要理解力学转导，需要工程设备能够在受控环境中提供对模拟活体中发现的组合机械载荷(压缩/拉伸)的系统可变外部机械刺激的反应的现场评估。在这个职业项目中，通过开发集成的微电子机械系统(MEMS)，将简化全自动细胞力学转导分析。该设备将通过最大限度地减少外部影响来简化细胞和组织的分析，并将在施加的机械刺激和关键的机械敏感生物分子的活性之间提供直接关联。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的组合机械信号应用于装载地点的电池。微流控网络的使用将允许大量细胞的并行激活，以及原位细胞间和细胞内分析。通过开发仪器和软件接口，将简化该设备的使用。该设备的效果将使用骨骼肌母细胞C2C12进行评估。通过实现定量研究机械训练路径，该设备将有助于研究控制机械敏感细胞的生理和病理条件的机制。职业项目将整合PI的研究、教育和外展活动。研究成果将被纳入课程和实验室模块，使工程领域和生物学领域的学生受益。这些研究发现将通过档案期刊和会议报告进行传播。与此同时，这项研究将提供一种工具，通过运动中的机构工程师计划向少数族裔和女性学生以及通过与当地高中合作向K-12学生传授数学、技术和工程科学，在一个令人兴奋的、实用的和互动的环境中。该项目的成果也将在实验室网站http://www.bme.ohio-state.edu/yizhao/.上获得

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/.