Department of Chemical and Systems Biology, Stanford University, Stanford, California.
Program in Biophysics, Stanford University, Stanford, California; Department of Biology and Howard Hughes Medical Institute, University of Washington, Seattle, Washington.
Biophys J. 2021 May 4;120(9):1578-1591. doi: 10.1016/j.bpj.2021.02.022. Epub 2021 Feb 23.
During actin-based cell migration, the actin cytoskeleton in the lamellipodium both generates and responds to force, which has functional consequences for the ability of the cell to extend protrusions. However, the material properties of the lamellipodial actin network and its response to stress on the timescale of motility are incompletely understood. Here, we describe a dynamic wrinkling phenotype in the lamellipodium of fish keratocytes, in which the actin sheet buckles upward away from the ventral membrane of the cell, forming a periodic pattern of wrinkles perpendicular to the cell's leading edge. Cells maintain an approximately constant wrinkle wavelength over time despite new wrinkle formation and the lateral movement of wrinkles in the cell frame of reference, suggesting that cells have a preferred or characteristic wrinkle wavelength. Generation of wrinkles is dependent upon myosin contractility, and their wavelength scales directly with the density of the actin network and inversely with cell adhesion. These results are consistent with a simple physical model for wrinkling in an elastic sheet under compression and suggest that the lamellipodial cytoskeleton behaves as an elastic material on the timescale of cell migration despite rapid actin turnover.
在肌动蛋白细胞迁移过程中,片状伪足中的肌动蛋白细胞骨架既能产生力,也能对力做出反应,这对细胞伸展突起的能力有重要的功能意义。然而,片状伪足的肌动蛋白网络的材料特性及其对运动时间尺度上的力的响应还不完全清楚。在这里,我们描述了鱼角膜细胞片状伪足中的一种动态褶皱表型,其中肌动蛋白片向上远离细胞的腹膜卷曲,形成与细胞前缘垂直的周期性褶皱图案。尽管新褶皱的形成和褶皱在细胞参考系中的横向移动,细胞仍能保持时间上的近似恒定的褶皱波长,这表明细胞具有一个优选或特征性的褶皱波长。褶皱的产生依赖于肌球蛋白的收缩性,其波长与肌动蛋白网络的密度直接相关,与细胞黏附力成反比。这些结果与在压缩下弹性片的简单物理褶皱模型一致,并表明尽管肌动蛋白周转率很快,但在细胞迁移的时间尺度上,片状伪足细胞骨架表现为一种弹性材料。