Article

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: 9.92). 07/2010; 20(13):1145-53. DOI: 10.1016/j.cub.2010.05.049
Source: PubMed

ABSTRACT 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.

Download full-text

Full-text

Available from: Margaret L Gardel, Aug 15, 2014
0 Followers
 · 
98 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Focal adhesion composition and size are modulated in a myosin II-dependent maturation process that controls adhesion, migration, and matrix remodeling. As myosin II activity drives stress fiber assembly and enhanced tension at adhesions simultaneously, the extent to which adhesion maturation is driven by tension or altered actin architecture is unknown. We show that perturbations to formin and α-actinin 1 activity selectively inhibited stress fiber assembly at adhesions but retained a contractile lamella that generated large tension on adhesions. Despite relatively unperturbed adhesion dynamics and force transmission, impaired stress fiber assembly impeded focal adhesion compositional maturation and fibronectin remodeling. Finally, we show that compositional maturation of focal adhesions could occur even when myosin II-dependent cellular tension was reduced by 80%. We propose that stress fiber assembly at the adhesion site serves as a structural template that facilitates adhesion maturation over a wide range of tensions. This work identifies the essential role of lamellar actin architecture in adhesion maturation.
    The Journal of Cell Biology 02/2012; 196(3):363-74. DOI:10.1083/jcb.201107042 · 9.69 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The regulation of cellular traction forces on the extracellular matrix is critical to cell adhesion, migration, proliferation, and differentiation. Diverse lamellar actin organizations ranging from contractile lamellar networks to stress fibers are observed in adherent cells. Although lamellar organization is thought to reflect the extent of cellular force generation, understanding of the physical behaviors of the lamellar actin cytoskeleton is lacking. To elucidate these properties, we visualized the actomyosin dynamics and organization in U2OS cells over a broad range of forces. At low forces, contractile lamellar networks predominate and force generation is strongly correlated to actomyosin retrograde flow dynamics with nominal change in organization. Lamellar networks build ∼60% of cellular tension over rapid time scales. At high forces, reorganization of the lamellar network into stress fibers results in moderate changes in cellular tension over slower time scales. As stress fibers build and tension increases, myosin band spacing decreases and α-actinin bands form. On soft matrices, force generation by lamellar networks is unaffected, whereas tension-dependent stress fiber assembly is abrogated. These data elucidate the dynamic and structural signatures of the actomyosin cytoskeleton at different levels of tension and set a foundation for quantitative models of cell and tissue mechanics.
    Molecular biology of the cell 02/2011; 22(8):1330-9. DOI:10.1091/mbc.E10-11-0891 · 5.98 Impact Factor
  • European Journal of Vascular Surgery 09/1988; 2(4):274. DOI:10.1016/S1051-0443(96)70118-5