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Single-cell response to stiffness exhibits muscle-like behavior

机译:单细胞对僵硬的反应表现出类似肌肉的行为

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摘要

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.
机译:活细胞感觉到环境的僵化并适应其活动。特别地,在弹性基底上培养的细胞沿最高刚度的方向排列其形状和牵引力,并优选向较硬的区域迁移。尽管许多研究调查了粘附复合物在刚度传感中的作用,但对于基于肌动蛋白的收缩力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变形刚度不同的偏斜成肌细胞微板的缩短速度。力的产生速率随刚度的增加而增加,并遵循希尔力-速度关系。因此,细胞对僵硬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。这些结果揭示了刚性感测的意想不到的机制,其中收缩的肌动球蛋白单位本身可以充当传感器。这种机制可以将基质刚度的各向异性转变为细胞骨架张力的各向异性,从而可以协调粘附复合物的局部活性并引导细胞沿着刚度梯度迁移。

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