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Coordination between Intra- and Extracellular Forces Regulates Focal Adhesion Dynamics

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posted on 19.12.2016 by Bibhu Ranjan Sarangi, Mukund Gupta, Bryant L. Doss, Nicolas Tissot, France Lam, René-Marc Mège, Nicolas Borghi, Benoît Ladoux
Focal adhesions (FAs) are important mediators of cell–substrate interactions. One of their key functions is the transmission of forces between the intracellular acto-myosin network and the substrate. However, the relationships between cell traction forces, FA architecture, and molecular forces within FAs are poorly understood. Here, by combining Förster resonance energy transfer (FRET)-based molecular force biosensors with micropillar-based traction force sensors and high-resolution fluorescence microscopy, we simultaneously map molecular tension across vinculin, a key protein in FAs, and traction forces at FAs. Our results reveal strong spatiotemporal correlations between vinculin tension and cell traction forces at FAs throughout a wide range of substrate stiffnesses. Furthermore, we find that molecular tension within individual FAs follows a biphasic distribution from the proximal (toward the cell nucleus) to distal end (toward the cell edge). Using super-resolution imaging, we show that such a distribution relates to that of FA proteins. On the basis of our experimental data, we propose a model in which FA dynamics results from tension changes along the FAs.

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