Department of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee, USA.
Department of Physics and Astronomy, Vanderbilt University, Nashville, Tennessee, USA.
Cytoskeleton (Hoboken). 2022 Sep;79(9-11):81-93. doi: 10.1002/cm.21722. Epub 2022 Sep 5.
Ventral stress fibers (VSFs) are contractile actin fibers dynamically attached to cell-matrix focal adhesions. VSFs are critical in cellular traction force production and migration. VSFs vary from randomly oriented short, thinner fibers to long, thick fibers that span along the whole long axis of a cell. De novo VSF formation was shown to occur by cortical actin mesh condensation or by crosslinking of dorsal stress fibers and transverse arcs at the cell front. However, the formation of long VSFs that extend across the whole cell axis is not well understood. Here, we report a novel phenomenon of VSF merging in migratory fibroblast cells, which is guided by mechanical force balance and contributes to VSF alignment along the long cell axis. The mechanism of VSF merging involves two steps: connection of two ventral fibers by an emerging myosin II bridge at an intervening adhesion and intervening adhesion dissolution. Our data indicate that these two steps are interdependent: slow adhesion disassembly leads to the slowing of the myosin bridge formation. Cellular data and computational modeling show that the contact angle between merging fibers decides successful merging, with shallow angles leading to merge failure. Our data and modeling further show that merging increases the share of uniformly aligned long VSFs, likely contributing to directional traction force production. Thus, we characterize merging as a process for dynamic reorganization of VSFs with functional significance for directional cell migration.
腹侧应力纤维(VSFs)是动态附着在细胞基质黏附斑上的收缩性肌动蛋白纤维。VSFs 在细胞牵引力产生和迁移中起着至关重要的作用。VSFs 从随机定向的短而细的纤维到长而粗的纤维变化,这些纤维沿着细胞的整个长轴延伸。新形成的 VSF 被证明是通过皮质肌动蛋白网格凝聚或通过背部应力纤维和细胞前缘的横向弧形的交联而发生的。然而,对于延伸穿过整个细胞轴的长 VSF 的形成还不是很清楚。在这里,我们报告了一个新的现象,即在迁移的成纤维细胞中 VSF 的合并,这是由机械力平衡引导的,并有助于 VSF 沿着长细胞轴的对齐。VSF 合并的机制涉及两个步骤:在中间黏附中通过新形成的肌球蛋白 II 桥连接两个腹侧纤维,以及中间黏附的溶解。我们的数据表明这两个步骤是相互依赖的:缓慢的黏附解体导致肌球蛋白桥的形成减缓。细胞数据和计算模型表明,合并纤维之间的接触角决定了合并的成功,较浅的角度导致合并失败。我们的数据和模型进一步表明,合并增加了均匀对齐的长 VSF 的份额,可能有助于产生定向牵引力。因此,我们将合并描述为一种具有动态重组 VSF 的过程,对定向细胞迁移具有功能意义。