Biophysics Graduate Program, University of Chicago, Chicago, Illinois, USA.
Biophys J. 2013 Apr 16;104(8):1709-19. doi: 10.1016/j.bpj.2013.01.017.
Dynamic regulation of the actin cytoskeleton is required for diverse cellular processes. Proteins regulating the assembly kinetics of the cytoskeletal biopolymer F-actin are known to impact the architecture of actin cytoskeletal networks in vivo, but the underlying mechanisms are not well understood. Here, we demonstrate that changes to actin assembly kinetics with physiologically relevant proteins profilin and formin (mDia1 and Cdc12) have dramatic consequences on the architecture and gelation kinetics of otherwise biochemically identical cross-linked F-actin networks. Reduced F-actin nucleation rates promote the formation of a sparse network of thick bundles, whereas increased nucleation rates result in a denser network of thinner bundles. Changes to F-actin elongation rates also have marked consequences. At low elongation rates, gelation ceases and a solution of rigid bundles is formed. By contrast, rapid filament elongation accelerates dynamic arrest and promotes gelation with minimal F-actin density. These results are consistent with a recently developed model of how kinetic constraints regulate network architecture and underscore how molecular control of polymer assembly is exploited to modulate cytoskeletal architecture and material properties.
细胞骨架的动态调节对于多种细胞过程是必需的。已知调节细胞骨架生物聚合物 F-肌动蛋白组装动力学的蛋白质会影响体内肌动蛋白细胞骨架网络的结构,但相关的潜在机制尚不清楚。在这里,我们证明了与生理相关的蛋白(原肌球蛋白和formin(mDia1 和 Cdc12))改变肌动蛋白组装动力学对其他生化上相同的交联 F-肌动蛋白网络的结构和凝胶动力学有巨大影响。F-肌动蛋白成核率的降低会促进厚束稀疏网络的形成,而成核率的增加则会导致更密集的薄束网络。F-肌动蛋白延伸率的变化也有显著的影响。在低延伸率下,凝胶停止,形成刚性束的溶液。相比之下,快速的丝状延伸加速了动态捕获并以最小的 F-肌动蛋白密度促进凝胶化。这些结果与最近提出的一种关于动力学约束如何调节网络结构的模型一致,并强调了如何利用聚合物组装的分子控制来调节细胞骨架结构和材料性能。