This work will advance our understanding of how cells process of mechanical signals. The effort is based upon Single-Cell-Pico-Force-Microscopy (SCPFM), a new instrument poised to become widely applicable to many studies in cell biology. SCPFM integrates near-single-molecule force measurement capabilities of Nano Electro Mechanical Systems (NEMS) with integrated microfluidics enabling precision fluid control, and thereby precision pharmacological stimulation, of individual cells. Understanding cellular force generation and regulation is critical to understanding many basic aspects of cell function; among these are: cell motility, cell division, and cell organization; many aspects of organism function: wound healing, inflammation, and embryogenesis; and numerous diseases, including many cancers and cardiovascular disease. Specifically, this work will investigate the compliance sensing and force response of the Extra-Cellular-Matrix (ECM) as a model system for studying the role of mechanics in cell regulation. SCPFM enables, for example, detailed and systematic study of the molecular-mechanical responses of individual lamellipodia to pharmacological and mechanical stimulation. Force-time records of compliance sensing and response events will be acquired in this work, and these will be used to assemble a library of molecular-mechanical force signatures with which to analyze the force-time records.
SCPFM combines device physics, nano-fabrication, and electrical engineering with surface chemistry, cell biology and biochemistry in a complex, interconnected system. This presents an extraordinary opportunity for graduate students and post-docs to become interdisciplinary scientists capable of leading and successfully integrating interdisciplinary teams and projects. Undergraduate and minority students will have the opportunity to be involved through Caltech?s SURF and MURF programs (Summer/Minority Undergraduate Research Fellowship). The impact of this research will be carried into the local community by the graduate students and post-docs involved in cooperation with Caltech?s Classroom Connection, which partners researchers with local high school science classes where they serve as role models for pre-college students.
