肌凝蛋白力重塑F-肌动蛋白的机械敏感蛋白识别，这一成果由洛克菲勒大学Gregory M. Alushin课题组经过不懈努力而取得。这一研究成果发表在2026年4月22日出版的国际学术期刊《自然》上。

在这里，研究小组发现肌凝蛋白产生的力引起肌动蛋白丝（F-actin）的结构变化，从而调节机械敏感粘附蛋白α-catenin的结合。通过相关的冷冻荧光显微镜和冷冻电子断层扫描，课题组人员发现F-actin在细胞骨架-粘附界面处具有纳米级振荡曲率的正弦区域，而zyxin是肌动蛋白-肌球蛋白产生牵引力的标志。该

课题组人员介绍了一种重建系统，用于在肌凝蛋白力的存在下可视化f -肌动蛋白，低温电子显微镜显示形态相似的F-肌动蛋白超级线圈。在模拟中，模拟肌球蛋白活性的压缩力产生超级线圈，这可以由异步马达的集合产生，而不管它们的方向如何。超线圈的三维重建揭示了F-肌动蛋白螺旋晶格的广泛不对称重塑。α-连环蛋白可以识别这一点，它沿着单个链协同结合，优先结合具有扩展亚基间距离的界面，同时抑制旋转偏差，使晶格正则化。总之，该团队发现肌球蛋白力可以使f -肌动蛋白变形，产生一种由机械敏感蛋白检测和相互调节的构象景观，从而提供了通过细胞骨架进行主动力转导的直接结构一瞥。

据介绍，细胞通过细胞骨架连接的粘附与周围环境机械地结合，这使它们能够感知指示发育和驱动癌症等疾病的物理信号。肌球蛋白运动蛋白产生的收缩力通过未知的蛋白质结构机制介导这些机械信号转导过程。

附：英文原文

Title: Myosin forces remodel F-actin for mechanosensitive protein recognition

Author: Carl, Ayala G., Reynolds, Matthew J., Sun, Xiaoyu, Gurel, Pinar S., Phua, Donovan Y. Z., Hamilton, Keith, Mei, Lin, Watters, John W., Takagi, Yasuharu, Noble, Alex J., Sellers, James R., Alushin, Gregory M.

Issue&Volume: 2026-04-22

Abstract: Cells interface mechanically with their surroundings through cytoskeleton-linked adhesions1,2, which enable them to sense physical cues that instruct development and drive diseases such as cancer3,4,5. Contractile forces generated by myosin motor proteins6,7 mediate these mechanical signal transduction processes through unknown protein structural mechanisms. Here we show that force generated by myosin elicits structural changes in actin filaments (F-actin) that modulate binding by the mechanosensitive adhesion protein α-catenin8. Using correlative cryo-fluorescence microscopy and cryo-electron tomography, we identify F-actin featuring sinusoidal regions of nanoscale oscillating curvature at cytoskeleton–adhesion interfaces enriched in zyxin, a marker of actin–myosin-generated traction forces9. We introduce a reconstitution system for visualizing F-actin in the presence of myosin forces using cryo-electron microscopy, which reveals morphologically similar F-actin supercoils. In simulations, compressive forces that mimic myosin activity produce supercoils, which can be generated by ensembles of asynchronous motors regardless of their directionality. Three-dimensional reconstruction of supercoils uncovers extensive asymmetric remodelling of the helical lattice of F-actin. This is recognized by α-catenin, which binds cooperatively along individual strands, preferentially engaging interfaces that feature extended inter-subunit distances while simultaneously suppressing rotational deviations to regularize the lattice. In sum, we find that myosin forces can deform F-actin, generating a conformational landscape that is detected and reciprocally modulated by a mechanosensitive protein, providing a direct structural glimpse at active force transduction through the cytoskeleton.

DOI: 10.1038/s41586-026-10398-7

Source: https://www.nature.com/articles/s41586-026-10398-7