Coordination between intra- and extra- cellular forces regulates focal adhesion dynamics. NANO LETTERS, December 2016.

By Bibhu Ranjan Sarangi, Mukund Gupta, Bryant L Doss, Nicolas Tissot, France Lam, René Marc Mege, Nicolas Borghi, and Benoit Ladoux

Nano Letters. December 2016. Epub ahead of print. doi: 10.1021/acs.nanolett.6b04364

Abstract

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 (towards the cell nucleus) to distal end (towards the cell edge). Using super-resolution imaging, we show that such a distribution relates to that of FA proteins. Based on our experimental data, we propose a model in which FA dynamics results from tension changes along the FAs.