Focal Contacts as Mechanosensors

By D. Riveline, E. Zamir, Nathalie Q. Balaban, Ulrich S. Schwarz, T. Ishizaki, S. Narumiya, Zvi Kam, Benjamin Geiger, A. Bershadsky. Journal of Cell Biology, 2001

1,487 citations recorded by the source corpus.

The transition of cell–matrix adhesions from the initial punctate focal complexes into the mature elongated form, known as focal contacts, requires GTPase Rho activity. In particular, activation of myosin II–driven contractility by a Rho target known as Rho-associated kinase (ROCK) was shown to be essential for focal contact formation. To dissect the mechanism of Rho-dependent induction of focal contacts and to elucidate the role of cell contractility, we applied mechanical force to vinculin-containing dot-like adhesions at the cell edge using a micropipette. Local centripetal pulling led to local assembly and elongation of these structures and to their development into streak-like focal contacts, as revealed by the dynamics of green fluorescent protein–tagged vinculin or paxillin and interference reflection microscopy. Inhibition of Rho activity by C3 transferase suppressed this force-induced focal contact formation. However, constitutively active mutants of another Rho target, the formin homology protein mDia1 (Watanabe, N., T. Kato, A. Fujita, T. Ishizaki, and S. Narumiya. 1999. Nat. Cell Biol. 1:136–143), were sufficient to restore force-induced focal contact formation in C3 transferase-treated cells. Force-induced formation of the focal contacts still occurred in cells subjected to myosin II and ROCK inhibition. Thus, as long as mDia1 is active, external tension force bypasses the requirement for ROCK-mediated myosin II contractility in the induction of focal contacts. Our experiments show that integrin-containing focal complexes behave as individual mechanosensors exhibiting directional assembly in response to local force.

Subfields: Cell Biology, Immunology and Allergy

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Citations in the corpus

The relationship between force and focal complex development (2002, methodology): “Because initial integrin–ECM connections (Choquet et al., 1997) and focal complexes (Riveline et al., 2001) are responsive to mechanical stimuli, we probed the relationship between the maturation of an initial adhesion into a focal complex and its ability to exert migration force using two…”
A distinctive role for focal adhesion proteins in three-dimensional cell motility (2010, background): “Focal adhesions, which contain more than 100 different proteins and have both mechanosensory and signalling function”
Analysis of the myosinII-responsive focal adhesion proteome reveals a role for β-Pix in negative regulation of focal adhesion maturation (2011, background): “Focal adhesions are mechanosensitive and in response to tension will grow, recruiting proteins and changing composition during maturatio”
Integrins and extracellular matrix in mechanotransduction. (2010, background): “At only slightly longer times, entire adhesions in adherent cells lengthen under applied force, indicating the recruitment of not only vinculin but integrins and other proteins (Riveline et al. 2001).”
Harnessing nanotopography and integrin-matrix interactions to influence stem cell fate. (2014, background): “on the local force exerted by a cell [4].”
Review on Cell Mechanics: Experimental and Modeling Approaches (2013, background): “Since then, microneedle manipulation techniques have been applied to study focal adhesion and adherens junction mechanotransduction [108] [109], structural connectivity between the cytoskeleton and nucleus [110], opening of stretch ion channels [111], and neuron growth under tensile forces [112]…”
Dynamic molecular processes mediate cellular mechanotransduction (2011, neutral): “Although the other molecular players are different, vinculin is recruited to both structures in a myosin-dependent manner, thereby contributing to adhesion strengthenin”
Mechanical control of stem cell differentiation (2008, background): “, 2003), which implies the development of stress within these structures, and these stresses regulate the assembly/disassembly of focal adhesions (Chrzanowska-Wodnicka and Burridge, 1996; Helfman et al., 1999; Balaban et al., 2001; Riveline et al., 2001; Sniadecki et al., 2007).”
Tensegrity I. Cell structure and hierarchical systems biology (2003, background): “Note that both application of mechanical force to cell-ECM adhesions (Riveline et al., 2001) and microtubule disruption (Liu et al., 1987) activate the Rho signaling pathway that leads to MLC phosphorylation.”
Tensegrity II. How structural networks influence cellular information processing networks (2003, background): “In addition, forces applied to integrins produce a stress-dependent increase in focal adhesion assembly that is mediated through the small GTPase, Rho (Riveline et al., 2001; Balaban et al., 2001; Galbraith et al., 2002), and the sustained response of endothelium to fluid shear stress appears to req”