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MEASURING PATTERNS, REGULATION, AND BIOLOGIC CONSEQUENCES OF CELLULAR TRACTION FORCES. 

L. Romer, Departments of Anesthesiology and Critical Care Medicine, Pediatrics, and Cell Biology, Johns Hopkins University School of Medicine, Baltimore, Maryland.

   The exchange of mechanical signals between mammalian cells and their extracellular matrix microenvironment is a focus of keen interest for biologists in the diverse fields of developmental organogenesis, vascular wall function, tissue engineering, and oncology.  The molecular machinery of cellular mechanical signal response includes at least three major components: transmembrane adhesion receptors for extracellular matrix; the microfilament and microtubule cytoskeletal systems; and regulatory elements including the Rho family of GTP-binding proteins that modulate the density and contraction state of cytoskeletal elements.  Complex signaling pathways link these three arms of mechanical signal response, and gravitational forces have been shown to alter some cytoskeletal dynamics.

   Arrays of microfabricated PDMS posts have provided a system for reporting the traction force at individual cell-matrix interaction sites.  Volumetric imaging of posts with known spring constants allows the efficient analysis of maps of cell traction force vectors and their coincidence with both actin polymerization and signal molecule localization.  We have defined unique patterns of force generation that are specific for cells of fibroblast, endothelial, epithelial, and smooth muscle lineages.  Additionally, the contributions of signaling molecules, including non-receptor tyrosine kinases and GTPases, to the geometry and magnitude of cell-matrix adhesion forces have been determined.  Cell-generated mechanical forces directly affect patterning of the matrix milieu and the mechanical cues that are stored in it.  These investigations have important implications for understanding and optimizing cellular growth behaviors during tissue development and repair.

(Supported by NIH and JHU-SOM FMD.)