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Propagation of Mechanical Stress through the Actin Cytoskeleton toward Focal Adhesions: Model and Experiment

Raja Paul ^*, Patrick Heil  , Joachim P. Spatz   and Ulrich S. Schwarz ^*

^* Bioquant, Department of Biophysical Chemistry, University of Heidelberg, Heidelberg, Germany; and Max Planck Institute for Metals Research, Department of New Materials and Biosystems, Stuttgart, Germany

Correspondence: Address reprint requests to Dr. Ulrich S. Schwarz, Tel.: 49-6221-54-51254; E-mail: ulrich.schwarz{at}bioquant.uni-heidelberg.de.

We investigate both theoretically and experimentally how stress is propagated through the actin cytoskeleton of adherent cells and consequentially distributed at sites of focal adhesions (FAs). The actin cytoskeleton is modeled as a two-dimensional cable network with different lattice geometries. Both prestrain, resulting from actomyosin contractility, and central application of external force, lead to finite forces at the FAs that are largely independent of the lattice geometry, but strongly depend on the exact spatial distribution of the FAs. The simulation results compare favorably with experiments with adherent fibroblasts onto which lateral force is exerted using a microfabricated pillar. For elliptical cells, central application of external force along the long axis leads to two large stress regions located obliquely opposite to the pulling direction. For elliptical cells pulled along the short axis as well as for circular cells, there is only one region of large stress opposite to the direction of pull. If in the computer simulations FAs are allowed to rupture under force for elliptically elongated and circular cell shapes, then morphologies arise which are typical for migrating fibroblasts and keratocytes, respectively. The same effect can be obtained also by internally generated force, suggesting a mechanism by which cells can control their migration morphologies.

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				I. B. Bischofs, F. Klein, D. Lehnert, M. Bastmeyer, and U. S. Schwarz Filamentous Network Mechanics and Active Contractility Determine Cell and Tissue Shape Biophys. J., October 1, 2008; 95(7): 3488 - 3496. [Abstract] [Full Text] [PDF]