Mechanobiology Institute, National University of Singapore, Singapore, 117411, Singapore.
Department of Physics, National University of Singapore, Singapore, 117542, Singapore.
Nat Commun. 2017 Nov 21;8(1):1650. doi: 10.1038/s41467-017-01745-4.
Formins, an important family of force-bearing actin-polymerizing factors, function as homodimers that bind with the barbed end of actin filaments through a ring-like structure assembled from dimerized FH2 domains. It has been hypothesized that force applied to formin may facilitate transition of the FH2 ring from an inhibitory closed conformation to a permissive open conformation, speeding up actin polymerization. We confirm this hypothesis for mDia1 dependent actin polymerization by stretching a single-actin filament in the absence of profilin using magnetic tweezers, and observe that increasing force from 0.5 to 10 pN can drastically speed up the actin polymerization rate. Further, we find that this force-promoted actin polymerization requires torsionally unconstrained actin filament, suggesting that mDia1 also senses torque. As actin filaments are subject to complex mechanical constraints in living cells, these results provide important insights into how formin senses these mechanical constraints and regulates actin organization accordingly.
成核因子是一类重要的力承载肌动蛋白聚合因子，作为同源二聚体发挥作用，通过由二聚化 FH2 结构域组装成的环状结构与肌动蛋白丝的帽状末端结合。据推测，作用于成核因子的力可能有助于 FH2 环从抑制性封闭构象向允许性开放构象转变，从而加速肌动蛋白聚合。我们通过使用磁镊在没有 Profilin 的情况下拉伸单个肌动蛋白丝来证实这个假设，观察到从 0.5 到 10 pN 的力增加可以极大地加快肌动蛋白聚合速率。此外，我们发现这种力促进的肌动蛋白聚合需要不受扭转约束的肌动蛋白丝，表明 mDia1 也能感知扭矩。由于肌动蛋白丝在活细胞中受到复杂的机械约束，这些结果为成核因子如何感知这些机械约束以及相应地调节肌动蛋白组织提供了重要的见解。
