Abstract
Myosin II motors drive changes in focal adhesion morphology and composition in a “maturation process” that is crucial for regulating adhesion dynamics and signaling guiding cell adhesion, migration and fate. The underlying mechanisms of maturation, however, have been obscured by the intermingled effects of myosin II on lamellar actin architecture, dynamics and force transmission. Here, we show that focal adhesion growth rate stays constant even when cellular tension is reduced by 75%. Focal adhesion growth halts only when myosin stresses are sufficiently low to impair actin retrograde flow. Focal adhesion lifetime is reduced at low levels of cellular tension, but adhesion stability can be rescued at low levels of force by over-expression of α-actinin or constitutively active Dia1. Our work identifies a minimal myosin activity threshold that is necessary to drive lamellar actin retrograde flow is sufficient to permit focal adhesion elongation. Above this nominal threshold, myosin-mediated actin organization and dynamics regulate focal adhesion growth and stability in a force-insensitive fashion.
Highlights
Cell adhesion to the extracellular matrix (ECM) is dynamically regulated during directed cell migration, tissue morphogenesis and wound healing [1,2]
While it is widely presumed that focal adhesion maturation is a tension-dependent process [2,8,10,11], several recent studies have implicated the importance of myosin II cross-linking and radial stress fiber assembly in focal adhesion growth [4,7]
Using live cell imaging to track focal adhesion dynamics and actin retrograde flow, we found that both the focal adhesion growth rate and actin retrograde flow rate stayed remarkably constant as tension was reduced by 75%
Summary
Cell adhesion to the extracellular matrix (ECM) is dynamically regulated during directed cell migration, tissue morphogenesis and wound healing [1,2]. Stresses generated by myosin II drive retrograde flow of the lamellar actin cytoskeleton and are transmitted to focal adhesion proteins, which are thought to respond in a force-dependent manner. Myosinmediated cross-linking facilitates reorganization of lamellar actin in a formin (Dia1) and a-actinin dependent manner to form a dense radial stress fiber (RSF) at the focal adhesion [4,7,8,9]. While it is widely presumed that focal adhesion maturation is a tension-dependent process [2,8,10,11], several recent studies have implicated the importance of myosin II cross-linking and radial stress fiber assembly in focal adhesion growth [4,7]. The extent to which mechanical tension is a direct regulator of focal adhesion growth and stabilization is not well established
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