Dresden 2014 – wissenschaftliches Programm

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BP: Fachverband Biologische Physik

BP 20: Cell adhesion, mechanics and migration I

BP 20.6: Hauptvortrag

Dienstag, 1. April 2014, 14:45–15:15, HÜL 386

Synthetic mechanobiology: Dissecting and rewiring force-based signaling — •Sanjay Kumar — University of California, Berkeley, USA

Living cells encounter a variety of mechanical signals encoded within their microenvironment, and these inputs can strongly regulate many fundamental cell and tissue behaviors. Here we present two complementary approaches we have recently created and applied to dissect and genetically manipulate this force-based signaling in living cells. First, we have used laser nanosurgery to spatially map the nanomechanical properties of actomyosin stress fibers. We have combined this approach with advanced molecular imaging tools (FRAP, FRET) to relate intracellular tensile forces to the conformational activation of mechanosensory proteins at the cell-extracellular matrix interface and the activities of specific myosin activators and isoforms. Second, we have used the tools of synthetic biology to precisely control the expression and activation of mechanoregulatory proteins in single cells using multiple mutually orthogonal inducer/repressor systems. This capability has enabled us to quantitatively elucidate relationships between signal activation and phenotype and to deconstruct complex signaling networks. In addition to improving our understanding of force-based signaling, these approaches are enabling us to "rewire" how cells communicate with their physical microenvironment, which we view as an important first step towards instructing cell behavior at interfaces between living and nonliving systems.