Adaptive rheology and ordering of cell cytoskeleton govern matrix rigidity sensing.
Adaptive rheology and ordering of cell cytoskeleton govern matrix rigidity sensing.
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DOI：
10.1038/ncomms8525
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发表时间：
2015-06-25
影响因子：
16.6
通讯作者：
Ladoux B
中科院分区：
文献类型：
--
作者：
Gupta M;Sarangi BR;Deschamps J;Nematbakhsh Y;Callan-Jones A;Margadant F;Mège RM;Lim CT;Voituriez R;Ladoux B
基质刚性传感调节多种细胞过程，对组织发育和疾病具有重要意义。然而，细胞如何探测基质刚性并因此对其做出反应仍不清楚。在这里，我们表明刚性感知和适应是从肌动蛋白细胞骨架重塑中自然产生的。我们的体外实验和理论模型证明了肌动蛋白细胞骨架的双相流变学，它从软基质上的流体转变为较硬基质上的固体。此外，我们发现基质刚度的增加与肌动蛋白应力纤维中取向顺序的出现相关，肌动蛋白应力纤维表现出各向同性到向列相的转变，我们在活性物质理论的框架中定量地表征了这一转变。这些发现暗示了在压力下肌动蛋白结构大规模增强所介导的机制，这可能是基质硬度依赖性细胞形状变化和细胞极性的机械驱动因素。
Matrix rigidity sensing regulates a large variety of cellular processes and has important implications for tissue development and disease. However, how cells probe matrix rigidity, and hence respond to it, remains unclear. Here, we show that rigidity sensing and adaptation emerge naturally from actin cytoskeleton remodeling. Our in vitro experiments and theoretical modeling demonstrate a bi-phasic rheology of the actin cytoskeleton, which transitions from fluid on soft substrates to solid on stiffer ones. Furthermore, we find that increasing substrate stiffness correlates with the emergence of an orientational order in actin stress fibers, which exhibit an isotropic to nematic transition that we characterize quantitatively in the framework of active matter theory. These findings imply mechanisms mediated by a large-scale reinforcement of actin structures under stress, which could be the mechanical drivers of substrate stiffness dependent cell shape changes and cell polarity.