title: Coordination between Intra- and Extracellular Forces Regulates Focal Adhesion Dynamics.
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 (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.
authors.affiliation: Institut Jacques Monod (IJM), CNRS UMR 7592 and University Paris Diderot , Paris, France.|SRM Research Institute and Department of Physics & Nanotechnology, SRM University , Kattankulathur, India.
authors.forename: Bibhu Ranjan
authors.initials: BR
authors.lastname: Sarangi
authors.affiliation: Mechanobiology Institute (MBI), National University of Singapore , Singapore.
authors.forename: Mukund
authors.initials: M
authors.lastname: Gupta
authors.affiliation: Mechanobiology Institute (MBI), National University of Singapore , Singapore.
authors.forename: Bryant L
authors.initials: BL
authors.lastname: Doss
authors.affiliation: Institut Jacques Monod (IJM), CNRS UMR 7592 and University Paris Diderot , Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Tissot
authors.affiliation: Institut Jacques Monod (IJM), CNRS UMR 7592 and University Paris Diderot , Paris, France.
authors.forename: France
authors.initials: F
authors.lastname: Lam
authors.affiliation: Institut Jacques Monod (IJM), CNRS UMR 7592 and University Paris Diderot , Paris, France.
authors.forename: René-Marc
authors.initials: RM
authors.lastname: Mège
authors.affiliation: Institut Jacques Monod (IJM), CNRS UMR 7592 and University Paris Diderot , Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Borghi
authors.affiliation: Institut Jacques Monod (IJM), CNRS UMR 7592 and University Paris Diderot , Paris, France.|Mechanobiology Institute (MBI), National University of Singapore , Singapore.
authors.forename: Benoît
authors.identifier: 0000-0003-2086-1556
authors.initials: B
authors.lastname: Ladoux
keywords: Mechanobiology; cell traction force; focal adhesion; micropillar substrate; molecular force sensor; rigidity sensing; vinculin