Department of Chemistry and Biochemistry, University of Maryland, College Park, MD 20742, USA.
J Phys Condens Matter. 2011 Sep 21;23(37):374101. doi: 10.1088/0953-8984/23/37/374101. Epub 2011 Aug 23.
Actin-based cell motility is essential to many biological processes. We built a simplified, three-dimensional computational model and subsequently performed stochastic simulations to study the growth dynamics of lamellipodia-like branched networks. In this work, we shed light on the antagonism between capping and anti-capping proteins in regulating actin dynamics in the filamentous network. We discuss detailed mechanisms by which capping and anti-capping proteins affect the protrusion speed of the actin network and the rate of nucleation of filaments. We computed a phase diagram showing the regimes of motility enhancement and inhibition by these proteins. Our work shows that the effects of capping and anti-capping proteins are mainly transmitted by modulation of the filamentous network density and local availability of monomeric actin. We discovered that the combination of the capping/anti-capping regulatory network with nucleation-promoting proteins introduces robustness and redundancy in cell motility machinery, allowing the cell to easily achieve maximal protrusion speeds under a broader set of conditions. Finally, we discuss distributions of filament lengths under various conditions and speculate on their potential implication for the emergence of filopodia from the lamellipodial network.
基于肌动蛋白的细胞运动对于许多生物过程至关重要。我们构建了一个简化的三维计算模型，并随后进行了随机模拟，以研究类似于片状伪足的分支网络的生长动态。在这项工作中，我们揭示了盖帽和反盖帽蛋白在调节丝状网络中肌动蛋白动力学方面的拮抗作用。我们讨论了详细的机制，即盖帽和反盖帽蛋白如何影响肌动蛋白网络的突起速度和纤维成核的速度。我们计算了一个相位图，显示了这些蛋白促进和抑制运动的范围。我们的工作表明，盖帽和反盖帽蛋白的作用主要通过调节丝状网络的密度和单体肌动蛋白的局部可用性来传递。我们发现，将盖帽/反盖帽调节网络与促进核形成的蛋白结合起来，可以为细胞运动机制提供鲁棒性和冗余性，从而使细胞能够在更广泛的条件下轻松实现最大的突起速度。最后，我们讨论了在各种条件下纤维长度的分布，并推测它们可能对从片状伪足网络中出现丝状伪足的潜在影响。
