United we stand - integrating the actin cytoskeleton and cell-matrix adhesions in cellular mechanotransduction

Advance Online Publication July 13, 2012 doi: 10.1242/?jcs.093716 July 1, 2012 J Cell Sci 125, 3051-3060. Ulrich S. Schwarz1,* and Margaret L. Gardel2,*

1BioQuant and Institute for Theoretical Physics, University of Heidelberg, Philosophenweg 19, 69120 Heidelberg, Germany

2Physics Department, James Franck Institute and Institute for Biophysical Dynamics, University of Chicago, Chicago, IL 60637, USA ?*Authors for correspondence (ulrich.schwarz{at}bioquant.uni-heidelberg.de; gardel{at}uchicago.edu) Many essential cellular functions in health and disease are closely linked to the ability of cells to respond to mechanical forces. In the context of cell adhesion to the extracellular matrix, the forces that are generated within the actin cytoskeleton and transmitted through integrin-based focal adhesions are essential for the cellular response to environmental clues, such as the spatial distribution of adhesive ligands or matrix stiffness. Whereas substantial progress has been made in identifying mechanosensitive molecules that can transduce mechanical force into biochemical signals, much less is known about the nature of cytoskeletal force generation and transmission that regulates the magnitude, duration and spatial distribution of forces imposed on these mechanosensitive complexes. By focusing on cell-matrix adhesion to flat elastic substrates, on which traction forces can be measured with high temporal and spatial resolution, we discuss our current understanding of the physical mechanisms that integrate a large range of molecular mechanotransduction events on cellular scales. Physical limits of stability emerge as one important element of the cellular response that complements the structural changes affected by regulatory systems in response to mechanical processes.

Key words Funding

U.S.S. is a member of the Heidelberg cluster of excellence CellNetworks and is supported by the BMBF MechanoSys grant [grant number 0315501C to U.S.S.]. M.L.G. is supported by a NIH Director's Pioneer Award [grant number DP10D00354], Packard Fellowship and Burroughs Wellcome Career Award. Deposited in PMC for release after 12 months.

This article is part of a Minifocus on Mechanotransduction. For further reading, please see related articles: ‘Deconstructing the third dimension – how 3D culture microenvironments alter cellular cues’ by Brendon M. Baker and Christopher S. Chen (J. Cell Sci. 125, 3015-3024). ‘Finding the weakest link – exploring integrin-mediated mechanical molecular pathways’ by Pere Roca-Cusachs et al. (J. Cell Sci. 125, 3025-3038). ‘Signalling through mechanical inputs – a coordinated process’ by Huimin Zhang and Michel Labouesse (J. Cell Sci. 125, 3039-3049). ‘Mechanosensitive mechanisms in transcriptional regulation’ by Akiko Mammoto et al. (J. Cell Sci. 125, 3061-3073). ‘Molecular force transduction by ion channels – diversity and unifying principles’ by Sergei Sukharev and Frederick Sachs (J. Cell Sci. 125, 3075-3083).

© 2012. Published by The Company of Biologists Ltd

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