The relationship between force and focal complex development

By C. Galbraith, Kenneth M. Yamada, M. Sheetz. Journal of Cell Biology, 2002

939 citations recorded by the source corpus.

To adhere and migrate, cells must be capable of applying cytoskeletal force to the extracellular matrix (ECM) through integrin receptors. However, it is unclear if connections between integrins and the ECM are immediately capable of transducing cytoskeletal contraction into migration force, or whether engagement of force transmission requires maturation of the adhesion. Here, we show that initial integrin–ECM adhesions become capable of exerting migration force with the recruitment of vinculin, a marker for focal complexes, which are precursors of focal adhesions. We are able to induce the development of focal complexes by the application of mechanical force to fibronectin receptors from inside or outside the cell, and we are able to extend focal complex formation to vitronectin receptors by the removal of c-Src. These results indicate that cells use mechanical force as a signal to strengthen initial integrin–ECM adhesions into focal complexes and regulate the amount of migration force applied to individual adhesions at localized regions of the advancing lamella.

Subfields: Atomic and Molecular Physics, and Optics, Cell Biology, Immunology and Allergy

View Paper: https://www.semanticscholar.org/paper/6996e41d129c94be67d1c72067f2769dadfa28de

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Citations in the corpus

Genetic and cell biological analysis of integrin outside-in signaling. (2009, background): “The application of external force to cells resulted in FA growth in several other studies (Riveline et al. 2001; Galbraith et al. 2002; Paul et al. 2008) and microscopic analysis found that adhesion formation was initiated during periodic contraction of actin in the lamellipodium (Giannone et al.”
Focal adhesion regulation of cell behavior. (2004, background): “This work provides a basis for later experiments demonstrating that the physical rigidity of the ECM can regulate focal adhesion formation [155,164–168].”
Non-muscle myosin II takes centre stage in cell adhesion and migration (2009, neutral): “For example, application of external forces produces post-translational modifications such as phosphorylation, or conformational changes in different signalling molecules, which inhibit protrusion formation and lead to adhesion maturation and actin filament bundlin”
Early molecular events in the assembly of matrix adhesions at the leading edge of migrating cells (2003, background): “, 1999b) or as a result of external mechanical perturbation (Galbraith et al., 2002; Riveline et al., 2001).”
Matrix density-induced mechanoregulation of breast cell phenotype, signaling, and gene expression through a FAK-ERK linkage (2009, neutral): “…external force to adhesions or exposure to a “stiff” two-dimensional substrate promotes FA size and strength (Choquet et al., 1997; Galbraith et al., 2002; Pelham & Wang, 1997; Sniadecki et al., 2007); and that Rho-dependent contractile force through the actin cytoskeleton promotes FA assembly…”
Activation of a vinculin‐binding site in the talin rod involves rearrangement of a five‐helix bundle (2004, background): “Since talin is clearly subject to the force exerted by actomyosin contraction, it is possible that stretch activates talin VBS1 allowing recruitment of vinculin and the matura- tion of small focal complexes into larger focal adhesions (Galbraith et al, 2002).”
Extracellular matrix rigidity governs smooth muscle cell motility in a biphasic fashion (2005, background): “…are in fact greater than those generated by larger, more mature adhesions (Beningo et al., 2001; Munevar et al., 2001) are contradicted by those reporting that smaller focal complexes formed at the leading edge of a motile cell exert smaller forces than focal adhesions (Galbraith et al., 2002).”
Balancing forces: architectural control of mechanotransduction (2011, neutral): “The application of external force can directly influence the shape, size and composition of focal adhesions, thereby demonstrating a direct correlation between force and biochemical signal generatio”
The myofibroblast: paradigm for a mechanically active cell. (2010, background): “This finding can explain how actin/myosin generated tension leads to the recruitment of vinculin to nascent adhesions (Delanoe-Ayari et al., 2004; Galbraith et al., 2002), an event that further strengthens the adhesion structure (Gallant et al.”
Cellular mechanotransduction: putting all the pieces together again (2006, background): “, focal adhesion remodeling and signaling) (17, 56, 76, 77, 100), the reality is that the whole cell is the mechanotransducer because it integrates these local signals with other environmental inputs before eliciting a specific behavioral response.”