Dawes Adriana T, Bard Ermentrout G, Cytrynbaum Eric N, Edelstein-Keshet Leah
Department of Mathematics, University of British Columbia, Vancouver, BC, Canada V6T 1Z2.
J Theor Biol. 2006 Sep 21;242(2):265-79. doi: 10.1016/j.jtbi.2006.02.017. Epub 2006 Apr 4.
We formulate and analyse a 1D model for the spatial distribution of actin density at the leading edge of a motile cell. The model incorporates nucleation, capping, growth and decay of actin filaments, as well as retrograde flow of the actin meshwork and known parameter values based on the literature. Using a simplified geometry, and reasonable assumptions about the biochemical processes, we derive PDEs for the density of actin filaments and their tips. Analytic travelling wave solutions are used to predict how the speed of the cell depends on rates of nucleation, capping, polymerization and membrane resistance. Analysis and simulations agree with experimental profiles for measured actin distributions. Extended versions of the model are studied numerically. We find that our model produces stable travelling wave solutions with reasonable cell speeds. Increasing the rate of nucleation of filaments (by the actin related protein Arp2/3) or the rate of actin polymerization leads to faster cell speed, whereas increasing the rate of capping or the membrane resistance reduces cell speed. We consider several variants of nucleation (spontaneous, tip, and side branching) and find best agreement with experimentally measured spatial profiles of filament and tip density in the side branching case.
我们构建并分析了一个关于运动细胞前缘肌动蛋白密度空间分布的一维模型。该模型纳入了肌动蛋白丝的成核、封端、生长和衰变,以及肌动蛋白网络的逆行流动,并基于文献给出了已知参数值。通过使用简化的几何结构以及对生化过程的合理假设,我们推导出了肌动蛋白丝及其末端密度的偏微分方程。解析行波解用于预测细胞速度如何依赖于成核、封端、聚合和膜阻力的速率。分析和模拟结果与实测肌动蛋白分布的实验曲线相符。对该模型的扩展版本进行了数值研究。我们发现我们的模型能产生具有合理细胞速度的稳定行波解。增加丝的成核速率(由肌动蛋白相关蛋白Arp2/3介导)或肌动蛋白聚合速率会导致细胞速度加快,而增加封端速率或膜阻力则会降低细胞速度。我们考虑了几种成核变体(自发、末端和侧向分支),并发现侧向分支情况下与实验测量的丝和末端密度空间曲线最为吻合。