CAREER: A Microsystems Approach to Cellular Manipulation and Interaction

本研究的目的是设计生物相容的微系统来研究细胞的生物力学和机械转导。 微尺度传感器和致动器提供了在细胞和分子水平上进行测量和操纵的潜力，具有前所未有的灵敏度，空间和时间分辨率。微系统将被开发来同时分析真实的时间内细胞的力学、电生理学和信号传导过程;这些研究目前不可能整合在一个单一的实验中。研究的目标包括：单细胞和细胞层在多轴力加载下的真实的时间研究，结合电生理测量，以及机电和信号测量装置集成到阵列中，为细胞和组织培养提供仪器化的、主动控制的支架。将启用新的基于组织的控制和测量，包括机械载荷、细胞变形、应变率以及跨组织的力和电环境的空间变化。更广泛的影响包括开发新的细胞和组织操作和测量工具，校准方法，以及用于体外生物力学和生化评估的微系统。机械耦合细胞培养系统将使人们对机械门控功能有新的认识，如骨生长、伤口愈合以及与机械感觉功能障碍有关的疾病，如动脉硬化和癌症--每年影响数百万美国人的疾病。将开发与细胞相互作用和操纵生物力学的微系统和方法。与分化、蛋白质表达和生物化学相关的细胞生物力学将被整合到可访问的数据库中。最终目标是开发机械活性基质，定制细胞发育以创建工程化活组织。

The objective of this research is to engineer biologically compatible microsystems to study biomechanics and mechanotransduction of cells. Microscale sensors and actuators offer the potential to make measurements and manipulate at cellular and molecular levels with unprecedented sensitivity, spatial and temporal resolution. Microsystems will be developed to analyze simultaneously the mechanics, electrophysiology, and signaling processes of cells in real time; studies which are currently impossible to integrate in a single experiment. Goals of the research include: the real time study of single cells and layers of cells under multi-axis force loading coupled with electophysiological measurements and the integration of electromechanical and signaling measurement devices into arrays providing instrumented, actively controlled scaffolding for cell and tissue culture. New tissue-based control and measurement will be enabled, including mechanical loading, cell deformations, strain rates, and spatial variation of forces and electrical environments across tissues. Broader impacts include development of new cellular and tissue manipulation and measurement tools, calibration methodologies, and microsystems for in vitro biomechanics and biochemical evaluation. Mechanically coupled cell culture systems will enable a new understanding of mechanically gated functions such as bone growth, wound healing, and diseases related to mechanosensory malfunction such as arteriosclerosis and cancer - diseases affecting millions of Americans each year. Microsystems and methods for interacting with cells and manipulating biomechanics will be developed. Cell biomechanics related to differentiation, protein expression, and biochemistry will be integrated into accessible databases. The ultimate goal is the development of mechanically active substrates tailoring cell development to create engineered living tissues.