Biophysical Society Thematic Meeting | Singapore

Mechanobiology of Disease

Thursday Speaker Abstracts

Single Molecule Force Measurements in Living Cells Reveal a Minimally Tensioned Integrin State Alexander Dunn . Stanford University, Stanford, CA, USA. Integrins mediate cell adhesion to the extracellular matrix and enable the construction of complex, multicellular organisms, yet fundamental aspects of integrin-based adhesion remain poorly understood. Notably, the magnitude of the mechanical load experienced by individual integrins within living cells is unclear, due principally to limitations inherent in existing techniques. Here we use FRET-based molecular tension sensors (MTSs) to directly measure the distribution of loads experienced by individual integrins in primary dermal fibroblasts. We find that the majority of integrins transmit relatively modest forces of less than 11 pN, and that a large minority bear loads of less than 3 pN. Our data also indicate that interactions with the fibronectin synergy site, a secondary binding site specifically for α5β1 integrin, lead to increased recruitment of α5β1 integrin to adhesions but not to an increase in overall cellular traction generation. Engagement with the synergy site does, however, increase cells’ resistance to detachment by externally applied loads. In total, these observations suggest that a substantial population of bound but minimally tensioned integrins may provide cells and tissues with physical resiliency in the presence of widely varying mechanical loads.

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