Transient Frictional Slip between Integrin and the ECM in Focal Adhesions under Myosin II Tension

Institute for Biophysical Dynamics, University of Chicago, Chicago, IL 60637, USA.
Current biology: CB (Impact Factor: 9.57). 07/2010; 20(13):1145-53. DOI: 10.1016/j.cub.2010.05.049
Source: PubMed


The spatiotemporal regulation of adhesion to the extracellular matrix is important in metazoan cell migration and mechanosensation. Although adhesion assembly depends on intracellular and extracellular tension, the biophysical regulation of force transmission between the actin cytoskeleton and extracellular matrix during this process remains largely unknown.
To elucidate the nature of force transmission as myosin II tension is applied to focal adhesions, we correlated the dynamics of focal adhesion proteins and the actin cytoskeleton to local traction stresses. Under low extracellular tension, newly formed adhesions near the cell periphery underwent a transient retrograde displacement preceding elongation. We found that myosin II-generated tension drives this mobility, and we determine the interface of differential motion, or "slip," to be between integrin and the ECM. The magnitude and duration of both adhesion slip and associated F-actin dynamics is strongly modulated by ECM compliance. Traction forces are generated throughout the slip period, and adhesion immobilization occurs at a constant tension.
We have identified a tension-dependent, extracellular "clutch" between integrins and the extracellular matrix; this clutch stabilizes adhesions under myosin II driven tension. The current work elucidates a mechanism by which force transmission is modulated during focal adhesion maturation.

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Available from: Margaret L Gardel, Aug 15, 2014
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    • "Without further analysis, it is impossible to ascertain whether the adhesion plaques are actually undergoing translocation or treadmilling. However, Arp2/3 inhibition reduces the coupling of adhesion plaques to the ECM to result in gross FA movements only typically seen during adhesion assembly [25] and disassembly [26]. "
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    • "Rac1 and Cdc42 activation at the leading edge drives the initial formation of small adhesions in an actin polymerization-dependent mechanism [23], [54]. RhoA is also localized to the leading edge and is activated spatiotemporally ahead of Rac1, but in contrast promotes the formation of contractile stress fibers resulting in the formation of large, long-lived FAs [32], [30], [56], [57]. CdGAP knockdown led to the formation of small FAs independent of matrix rigidity, suggesting that FAs in cdGAP RNAi-treated cells may have failed to mature due to decreased RhoA activity and/or the failure to activate downstream RhoA effectors such as ROCK or non-muscle myosin IIA. "
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    • "However, these movements are on a very short, sub-micron spatial scale, and so we do not include them in the model. Adhesions are multi-component protein complexes, whose content and properties depend on many factors and on the stage of their dynamics [5] [36] [37]. However, the detailed morphological cycle of adhesion maturation and turnover is beyond the scope of the current study, as there is little understanding of respective mechanical changes. "
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