Institute for Biophysical Dynamics, University of Chicago, Chicago, IL 60637, USA.
Curr Biol. 2010 Jul 13;20(13):1145-53. doi: 10.1016/j.cub.2010.05.049. Epub 2010 Jun 10.
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.
细胞外基质黏附的时空调节在多细胞生物的细胞迁移和机械感受中很重要。尽管黏附组装依赖于细胞内和细胞外张力,但在这个过程中,肌球蛋白 II 张力施加到黏附点时,细胞外基质和细胞骨架之间的力传递的生物物理调节在很大程度上仍然未知。
为了阐明力传递的性质,我们将黏附点蛋白和肌动球蛋白细胞骨架的动力学与局部牵引力相关联。在低细胞外张力下,细胞边缘附近新形成的黏附体会在伸长之前经历短暂的逆行位移。我们发现肌球蛋白 II 产生的张力驱动了这种迁移,并且我们确定了不同运动或“滑动”的界面是整合素和细胞外基质之间的界面。黏附滑动和相关 F-肌动蛋白动力学的幅度和持续时间都强烈受到细胞外基质顺应性的调节。在滑动期间会产生牵引力,并且在恒定张力下黏附会固定。
我们已经确定了整合素和细胞外基质之间的一种依赖于张力的细胞外“离合器”;在肌球蛋白 II 驱动的张力下,这种离合器稳定了黏附。目前的工作阐明了在黏附点成熟过程中力传递如何被调节的机制。