CAREER: A Microsystems Approach to Cellular Manipulation and Interaction

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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.