Single-cell response to stiffness exhibits muscle-like behavior
Single-cell response to stiffness exhibits muscle-like behavior
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DOI：
10.1073/pnas.0903994106
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发表时间：
2009-10-27
影响因子：
11.1
通讯作者：
Asnacios, Atef
中科院分区：
文献类型：
--
作者：
Mitrossilis, Demosthene;Fouchard, Jonathan;Asnacios, Atef
活细胞感知其环境的刚性并使其活动适应于该刚性。特别地，在弹性基底上培养的细胞使其形状和其牵引力沿着最高刚性的方向排列，并且优选地向更刚性的区域迁移。虽然许多研究探讨了粘附复合物在刚性传感中的作用，但对基于肌动蛋白的收缩性的具体贡献知之甚少。在这里，我们使用了定制的单细胞技术来测量牵引力，以及缩短的速度，孤立的成肌细胞偏转可变刚度的微孔板。力的产生率随着刚度的增加而增加，并且遵循Hill力-速度关系。因此，细胞对刚度的反应类似于肌肉对负荷的适应，反映了肌球蛋白与肌动蛋白结合的力依赖性动力学。这些结果揭示了一个意想不到的机制，刚性传感，从而收缩肌动球蛋白单位本身可以作为传感器。这一机制可能将基质刚性的各向异性转化为细胞骨架张力的各向异性，从而协调粘附复合物的局部活性并引导细胞沿着刚性梯度迁移。
Living cells sense the rigidity of their environment and adapt their activity to it. In particular, cells cultured on elastic substrates align their shape and their traction forces along the direction of highest stiffness and preferably migrate towards stiffer regions. Although numerous studies investigated the role of adhesion complexes in rigidity sensing, less is known about the specific contribution of acto-myosin based contractility. Here we used a custom-made single-cell technique to measure the traction force as well as the speed of shortening of isolated myoblasts deflecting microplates of variable stiffness. The rate of force generation increased with increasing stiffness and followed a Hill force-velocity relationship. Hence, cell response to stiffness was similar to muscle adaptation to load, reflecting the force-dependent kinetics of myosin binding to actin. These results reveal an unexpected mechanism of rigidity sensing, whereby the contractile acto-myosin units themselves can act as sensors. This mechanism may translate anisotropy in substrate rigidity into anisotropy in cytoskeletal tension, and could thus coordinate local activity of adhesion complexes and guide cell migration along rigidity gradients.