Mechanobiology Institute, National University of Singapore , Singapore 117411.
Department of Physics , National University of Singapore , Singapore 117542.
Nano Lett. 2018 Aug 8;18(8):5239-5247. doi: 10.1021/acs.nanolett.8b02211. Epub 2018 Jul 10.
Self-assembling actin filaments not only form the basis of the cytoskeleton network in cells but also are utilized as nanosized building blocks to make novel active matter in which the dynamic polymerization and depolymerization of actin filaments play a key role. Formins belong to a main family of actin nucleation factors that bind to the barbed end of actin filaments and regulate actin polymerization through an interaction with profilin. Due to actomyosin contractility and relative rotation between formin and actin filaments, formin-dependent actin polymerization is subject to force and rotation constraints. However, it remains unclear how force and rotation constraints affect formin-dependent actin polymerization in the presence of profilin. Here, we show that for rotation-unconstrained actin filaments, elongation is accelerated by both force and profilin. The combined effect leads to surprisingly fast actin elongation that can approach the diffusion-limited rate at forces of a few piconewtons. The elongation of rotation-constrained filaments is also accelerated by profilin but is insensitive to applied force. We show that FH2, the main actin binding domain, plays the primary mechanosensing role. Together, the findings not only significantly advance our understanding of the mechanochemical regulation of formin-mediated actin polymerization in cells but also can potentially be utilized to make novel actin-based active matter.
自我组装的肌动蛋白丝不仅构成了细胞骨架网络的基础，而且还被用作纳米级构建块，用于制造新型活性物质，其中肌动蛋白丝的动态聚合和去聚合起着关键作用。formin 属于肌动蛋白成核因子的主要家族之一，它与肌动蛋白丝的帽状末端结合，并通过与 Profilin 的相互作用来调节肌动蛋白聚合。由于肌球蛋白收缩和 formin 与肌动蛋白丝之间的相对旋转，formin 依赖性肌动蛋白聚合受到力和旋转的约束。然而，目前尚不清楚在 Profilin 存在的情况下，力和旋转约束如何影响 formin 依赖性肌动蛋白聚合。在这里，我们表明对于旋转不受约束的肌动蛋白丝，力和 Profilin 都可以加速伸长。这种联合效应导致肌动蛋白的伸长非常快，在几皮牛顿的力下可以接近扩散限制的速率。Profilin 也可以加速旋转约束的纤维的伸长，但对施加的力不敏感。我们表明，主要的肌动蛋白结合结构域 FH2 起着主要的机械传感作用。总之，这些发现不仅显著提高了我们对细胞中 formin 介导的肌动蛋白聚合的机械化学调节的理解，而且还可以潜在地用于制造新型基于肌动蛋白的活性物质。
