Mechanosensitive subcellular rheostasis drives emergent single-cell mechanical homeostasis.
Mechanosensitive subcellular rheostasis drives emergent single-cell mechanical homeostasis.
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DOI：
10.1038/nmat4654
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发表时间：
2016-09
期刊：
影响因子：
41.2
通讯作者：
Fu J
中科院分区：
文献类型：
--
作者：
Weng S;Shao Y;Chen W;Fu J
机械稳态是细胞在环境扰动下维持稳定状态的基本过程，由两种亚细胞机械传感器调节：细胞骨架张力和整合素介导的局灶黏附（FAs）。在这里，我们表明单细胞的机械稳态是由亚细胞骨架张力和FAs的不同的、渐进的动态（流变）共同驱动的。这种流变涉及一种机械敏感模式，其中细胞骨架张力和FA的基态通过松弛或强化来决定它们不同的反应路径。细胞骨架的药理学扰动和分子调节的整合素捕获-滑动键会导致FAs的变异性和诱导非稳态，但不会导致细胞骨架张力的非稳态，这表明FAs在调节稳态方面具有独特的敏感性。理论模型揭示了肌球蛋白介导的细胞骨架收缩性和FAs和细胞骨架中的捕获-滑移-键样行为是定量再现机械敏感性流变的充分和必要机制。我们的发现强调了以前被低估的细胞机械稳态的物理性质。
Mechanical homeostasis - a fundamental process by which cells maintain stable states under environmental perturbations - is regulated by two subcellular mechanotransducers: cytoskeleton tension and integrin-mediated focal adhesions (FAs). Here, we show that single-cell mechanical homeostasis is collectively driven by the distinct, graduated dynamics (rheostasis) of subcellular cytoskeleton tension and FAs. Such rheostasis involves a mechanosensitive pattern wherein ground states of cytoskeleton tension and FA determine their distinct reactive paths via either relaxation or reinforcement. Pharmacological perturbations of the cytoskeleton and molecularly modulated integrin catch-slip bonds biased the rheostasis and induced non-homeostasis of FAs, but not of cytoskeleton tension, suggesting a unique sensitivity of FAs in regulating homeostasis. Theoretical modeling revealed myosin-mediated cytoskeleton contractility and catch-slip-bond-like behaviors in FAs and the cytoskeleton as sufficient and necessary mechanisms for quantitatively recapitulating mechanosensitive rheostasis. Our findings highlight previously underappreciated physical nature of the mechanical homeostasis of cells.