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.

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机械刺激对脯氨酸和福尔马林介导的肌动蛋白聚合的影响

自组装肌动蛋白丝不仅构成细胞中细胞骨架网络的基础，而且还被用作纳米级结构单元，以制造新型活性物质，其中肌动蛋白丝的动态聚合和解聚作用起着关键作用。Formins属于肌动蛋白成核因子的主要家族，其与肌动蛋白丝的带刺末端结合，并通过与肌动蛋白蛋白的相互作用来调节肌动蛋白的聚合。由于肌动球蛋白的收缩性以及formin和actin丝之间的相对旋转，formin依赖的actin聚合会受到力和旋转的约束。然而，尚不清楚在存在脯氨酸蛋白的情况下，力和旋转约束如何影响形式依赖性肌动蛋白的聚合反应。在这里，我们表明对于不受旋转限制的肌动蛋白丝，力和纤维蛋白原均加速了伸长。结合的作用导致令人惊讶的快速肌动蛋白伸长，其在几微微牛顿的力下可以达到扩散受限的速率。脯氨酸蛋白也可限制旋转的长丝的伸长，但对施加的力不敏感。我们表明，FH2，主要的肌动蛋白结合域，起着主要的机械传感作用。在一起，这些发现不仅大大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控的理解，而且还可以潜在地用于制造新型的基于肌动蛋白的活性物质。脯氨酸蛋白也可限制旋转的长丝的伸长，但对施加的力不敏感。我们表明，FH2，主要的肌动蛋白结合域，起着主要的机械传感作用。在一起，这些发现不仅大大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控的理解，而且还可以潜在地用于制造新型的基于肌动蛋白的活性物质。脯氨酸蛋白也可限制旋转的长丝的伸长，但对施加的力不敏感。我们表明，FH2，主要的肌动蛋白结合域，起着主要的机械传感作用。在一起，这些发现不仅大大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控的理解，而且还可以潜在地用于制造新型的基于肌动蛋白的活性物质。