Grimm H P, Verkhovsky A B, Mogilner A, Meister J-J
Cellular Biophysics and Biomechanics Laboratory, Swiss Federal Institute of Technology, 1015 Lausanne, Switzerland.
Eur Biophys J. 2003 Sep;32(6):563-77. doi: 10.1007/s00249-003-0300-4. Epub 2003 May 9.
Leading edge protrusion is one of the critical events in the cell motility cycle and it is believed to be driven by the assembly of the actin network. The concept of dendritic nucleation of actin filaments provides a basis for understanding the organization and dynamics of the actin network at the molecular level. At a larger scale, the dynamic geometry of the cell edge has been described in terms of the graded radial extension model, but this level of description has not yet been linked to the molecular dynamics. Here, we measure the graded distribution of actin filament density along the leading edge of fish epidermal keratocytes. We develop a mathematical model relating dendritic nucleation to the long-range actin distribution and the shape of the leading edge. In this model, a steady-state graded actin distribution evolves as a result of branching, growth and capping of actin filaments in a finite area of the leading edge. We model the shape of the leading edge as a product of the extension of the actin network, which depends on actin filament density. The feedback between the actin density and edge shape in the model results in a cell shape and an actin distribution similar to those experimentally observed. Thus, we explain the stability of the keratocyte shape in terms of the self-organization of the branching actin network.
前沿突出是细胞运动周期中的关键事件之一，据信它是由肌动蛋白网络的组装驱动的。肌动蛋白丝的树突状成核概念为在分子水平上理解肌动蛋白网络的组织和动力学提供了基础。在更大尺度上，细胞边缘的动态几何形状已根据分级径向延伸模型进行了描述，但这种描述水平尚未与分子动力学联系起来。在这里，我们测量了鱼表皮角质形成细胞前沿肌动蛋白丝密度的分级分布。我们开发了一个数学模型，将树突状成核与远程肌动蛋白分布以及前沿形状联系起来。在这个模型中，稳态分级肌动蛋白分布是由于前沿有限区域内肌动蛋白丝的分支、生长和封端而演变而来的。我们将前沿形状建模为肌动蛋白网络延伸的产物，而这又取决于肌动蛋白丝密度。模型中肌动蛋白密度和边缘形状之间的反馈导致了与实验观察到的细胞形状和肌动蛋白分布相似的结果。因此，我们根据分支肌动蛋白网络的自组织来解释角质形成细胞形状的稳定性。
