论文标题
肌动蛋白驱动的细胞突起，细胞极化和爬行的棒滑滑模型
Stick-Slip model for actin-driven cell protrusions, cell polarisation and crawling
论文作者
论文摘要
细胞爬行需要细胞骨架产生细胞内力，并通过特定的粘附分子传播到细胞外底物。爬行细胞显示出令人兴奋的系统的许多特征，例如在没有外部提示的情况下自发对称性破裂和爬行，以及周期性和传播活性波。已经调用了活性细胞骨架网络中的机械不稳定性和激活因子的生化网络中的反馈回路和细胞骨架动力学的阻遏物，以解释这些动力学特征。在这里，我们表明，细胞基底粘附的动力学与线性细胞力学之间的相互作用足以再现在扩散和爬行细胞中观察到的许多非线性动力学模式。使用由局部机械力调节的细胞粘附分子离合器模型的分析形式主义，我们表明细胞牵引力表现出粘性滑移动力学，导致周期性的突出/缩回/缩回和沿细胞边缘传播波的波浪。这可以解释扩散细胞的自发对称性断裂和极化，从而导致稳定的爬行或双皮运动，以及持续的细胞运动需要足够强的瞬态外部刺激。该模型还突出了膜张力在提供对称性破裂所需的单元格之间的远程机械通信方面的作用。
Cell crawling requires the generation of intracellular forces by the cytoskeleton and their transmission to an extracellular substrate through specific adhesion molecules. Crawling cells show many features of excitable systems, such as spontaneous symmetry breaking and crawling in the absence of external cues, and periodic and propagating waves of activity. Mechanical instabilities in the active cytoskeleton network and feedback loops in the biochemical network of activators and repressors of cytoskeleton dynamics have been invoked to explain these dynamical features. Here, we show that the interplay between the dynamics of cell-substrate adhesion and linear cellular mechanics is sufficient to reproduce many non-linear dynamical patterns observed in spreading and crawling cells. Using an analytical formalism of the molecular clutch model of cell adhesion, regulated by local mechanical forces, we show that cellular traction forces exhibit a stick-slip dynamics resulting in periodic waves of protrusion/retraction and propagating waves along the cell edge. This can explain spontaneous symmetry breaking and polarisation of spreading cells, leading to steady crawling or bipedal motion, and bistability, where persistent cell motion requires a sufficiently strong transient external stimulus. The model also highlight the role of membrane tension in providing the long-range mechanical communication across the cell required for symmetry breaking.
