Cell mechanosensitivity controls the anisotropy of focal adhesions

doi:10.1073/pnas.0403539101

Cell mechanosensitivity controls the anisotropy of focal adhesions

Departments of ^*Materials and Interfaces and ^‡Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel

Edited by Thomas D. Pollard, Yale University, New Haven, CT, and approved July 8, 2004 (received for review May 19, 2004)

Abstract

Cellular adhesions are modulated by cytoskeletal forces or external stresses and adapt to the mechanical properties of the extracellular matrix. We propose that this mechanosensitivity can be driven at least in part by the elastic, cell-contractility-induced deformations of protein molecules that form the adhesion. The model accounts for observations of anisotropic growth and shrinkage of focal adhesions in the direction of the force and predicts that focal adhesions only grow within a range of force that is determined by the composition and matrix properties. This prediction is consistent with the observations of a force threshold for the appearance of elongated focal adhesions and the disruption of adhesions into fibrils on a mobile extracellular matrix. The growth dynamics is calculated and the predicted sliding of focal adhesions is consistent with several experiments.

Footnotes

↵ † To whom correspondence should be sent at the present address: Centre de Recherche Paul Pascal, Avenue Albert Schweitzer, 33600 Pessac, France. E-mail: nicolas{at}crpp-bordeaux.chrs.fr.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations: FA, focal adhesion; FX, focal complex.
↵ § The front and back edges of the adhesion are defined relative to the direction of the force induced by stress fibers. They should not be confused with the front and back of a moving cell (see Fig. 1).
↵ ¶ This assumption can be tested experimentally by time-resolved experiments in which integrins and a plaque protein are tagged separately (3). Double immunofluorescence of actin and vinculin already shows that the density of the stress fibers decreases at the edges of the adhesion (B. Zimerman and B.G., unpublished data).