Institute for Biophysical Dynamics, James Franck Institute, University of Chicago, Chicago, Illinois, United States of America.
PLoS One. 2013 Jul 29;8(7):e70652. doi: 10.1371/journal.pone.0070652. Print 2013.
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.
肌球蛋白 II 分子马达驱动着细胞黏附形态和组成的改变，这一“成熟过程”对于调节细胞黏附的动态变化以及细胞黏附、迁移和命运的信号转导至关重要。然而，由于肌球蛋白 II 对片状肌动蛋白结构、动力学和力传递的混合影响，成熟的潜在机制一直难以捉摸。在这里，我们发现，即使细胞张力降低 75%，黏附点的生长速率也保持不变。只有当肌球蛋白的张力足够低，从而阻碍了肌动蛋白的逆行流动时，黏附点的生长才会停止。在较低的细胞张力下，黏附点的寿命会缩短，但通过过表达 α-辅肌动蛋白或组成性激活 Dia1，在较低的力水平下可以挽救黏附的稳定性。我们的工作确定了一个最小的肌球蛋白活性阈值，该阈值足以驱动片状肌动蛋白的逆行流动，从而允许黏附点的延伸。在这个名义阈值之上，肌球蛋白介导的肌动蛋白组织和动力学以一种力不敏感的方式调节黏附点的生长和稳定性。
