CAREER: Regulation of multicellular behavior with an extracellular matrix signaling scaffold

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1150467Smith, MichaelThe research objectives of this Faculty Early Career Development (CAREER) project are to determine whether multicellular cultures in both 2D and 3D systems spatially regulate the tension in their extracellular matrix fibronectin fibers in a manner that would spatially control cell behavior and to determine how mechanical forces applied to these matrix fibers in turn regulate the proliferation and directed migration of cells resident within the matrix. The coordination of multicellular behavior is critical to numerous physiological processes such as morphogenesis and wound repair. Although soluble signaling molecules are known to regulate cell behavior over long distances, this project will explore how mechanical tension alters the structure of insoluble proteins that constitute the extracellular matrix. The highly interdisciplinary and integrative nature of this research will have a transformative impact on a number of fields since cell-cell communication is a basic scientific phenomenon that is critical to numerous aspects of cell biology and physiology. This hypothesis leads to the concept of an insoluble signaling scaffold that can be actively and reversibly tuned by cell contractility and will generate numerous testable hypotheses that upend traditionally held views about cell-cell communication in development, homeostasis, and disease. The multi-level education plan of this CAREER project includes development of a one hour, hands-on activity on cell mechanics that is intended to illustrate the role of scientists and engineers in tackling important societal problems to area high school students and development of a new graduate course entitled Cell Mechanics, Adhesion, and Locomotion, which will cover mechanics from molecular to multicellular length scales.