Ryan Gillian L, Holz Danielle, Yamashiro Sawako, Taniguchi Daisuke, Watanabe Naoki, Vavylonis Dimitrios
Department of Physics, Kettering University, 1700 University Avenue, Flint, Michigan, 48504.
Department of Physics, Lehigh University, 16 Memorial Drive East, Bethlehem, Pennsylvania, 18105.
Cytoskeleton (Hoboken). 2017 Dec;74(12):490-503. doi: 10.1002/cm.21389. Epub 2017 Aug 21.
Animal cells that spread onto a surface often rely on actin-rich lamellipodial extensions to execute protrusion. Many cell types recently adhered on a two-dimensional substrate exhibit protrusion and retraction of their lamellipodia, even though the cell is not translating. Travelling waves of protrusion have also been observed, similar to those observed in crawling cells. These regular patterns of protrusion and retraction allow quantitative analysis for comparison to mathematical models. The periodic fluctuations in leading edge position of XTC cells have been linked to excitable actin dynamics using a one-dimensional model of actin dynamics, as a function of arc-length along the cell. In this work we extend this earlier model of actin dynamics into two dimensions (along the arc-length and radial directions of the cell) and include a model membrane that protrudes and retracts in response to the changing number of free barbed ends of actin filaments near the membrane. We show that if the polymerization rate at the barbed ends changes in response to changes in their local concentration at the leading edge and/or the opposing force from the cell membrane, the model can reproduce the patterns of membrane protrusion and retraction seen in experiment. We investigate both Brownian ratchet and switch-like force-velocity relationships between the membrane load forces and actin polymerization rate. The switch-like polymerization dynamics recover the observed patterns of protrusion and retraction as well as the fluctuations in F-actin concentration profiles. The model generates predictions for the behavior of cells after local membrane tension perturbations.
铺展在表面的动物细胞通常依靠富含肌动蛋白的片状伪足延伸来实现细胞突出。许多最近黏附在二维基质上的细胞类型，即使细胞没有发生迁移，也会表现出片状伪足的突出和回缩。还观察到了突出的行波，类似于在爬行细胞中观察到的情况。这些突出和回缩的规律模式允许进行定量分析，以便与数学模型进行比较。利用肌动蛋白动力学的一维模型，将XTC细胞前缘位置的周期性波动与可兴奋的肌动蛋白动力学联系起来，该模型是细胞弧长的函数。在这项工作中，我们将这个早期的肌动蛋白动力学模型扩展到二维（沿着细胞的弧长和径向），并纳入一个模型膜，该膜会根据膜附近肌动蛋白丝自由倒刺端数量的变化而突出和回缩。我们表明，如果倒刺端的聚合速率响应于其在前缘的局部浓度变化和/或来自细胞膜的相反力而变化，该模型可以重现实验中观察到的膜突出和回缩模式。我们研究了膜负载力与肌动蛋白聚合速率之间的布朗棘轮和开关式力-速度关系。开关式聚合动力学恢复了观察到的突出和回缩模式以及F-肌动蛋白浓度分布的波动。该模型对局部膜张力扰动后细胞的行为产生了预测。
