Transfer Grant: Systems Biophysics of Multiscale State Transitions in Cells and Tissues

SYSTEMS BIOPHYSICS OF MULTISCALE STATE TRANSITIONS IN CELLS AND TISSUES - PROJECT SUMMARY OUR LAB DEVELOPS AND APPLIES INTEGRATED EXPERIMENTAL AND COMPUTATIONAL METHODS TO ELUCIDATE THE IMPACT OF MECHANICS ON BIOLOGY AT MULTIPLE SCALES. OUR GOAL FOR THE NEXT FEW YEARS IS TO UNCOVER HOW THE INTERPLAY OF COMPLEX BIOPHYSICAL FACTORS IN THE TISSUE MICROENVIRONMENT DRIVES STRUCTURAL AND FUNCTIONAL STATE TRANSITIONS AT THE CYTOSKELETAL, CELLULAR, AND TISSUE LEVELS. IN PARTICULAR, WE WILL FOCUS ON THE INTERPLAY BETWEEN OSMOTIC PRESSURE, EXTRACELLULAR MATRIX (ECM) CROSSLINKING, AND MESOSCALE ECM ARCHITECTURES. THESE FACTORS ARE PROMINENT IN TISSUES AND OFTEN SIMULTANEOUSLY PRESENT, BUT THEIR FUNDAMENTAL INTEGRATED IMPACT ON CELLULAR SYSTEMS IS NOT WELL UNDERSTOOD. WE WILL INVESTIGATE HOW TOGETHER THEY ACT AS INPUTS THAT PROGRAM LOCAL MOLECULAR AND CELLULAR INTERACTIONS. WE WILL EXTRACT THE CRITICAL INPUT PARAMETER VALUES THAT INDUCE DRASTIC MODE SWITCHING, ESPECIALLY IN CYTOSKELETAL ORGANIZATION AND FUNCTION, CELL MIGRATION, CELL-MATRIX INTERACTIONS, AND COLLECTIVE CELL DISSEMINATION. WE WILL DETERMINE THE MECHANISMS AND CONSEQUENCES OF BIOPHYSICAL TRANSITIONS AT DIFFERENT SCALES AND HOW THEY FUNCTION AS ON AND OFF SWITCHES FOR GLOBAL TISSUE PHENOTYPES.