Cellular Mechanotransduction: From Tension to Function.
Cellular Mechanotransduction: From Tension to Function.
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DOI：
10.3389/fphys.2018.00824
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发表时间：
2018
影响因子：
4
通讯作者：
Forte G
中科院分区：
文献类型：
--
作者：
Martino F;Perestrelo AR;Vinarský V;Pagliari S;Forte G
活细胞不断受到周围细胞外基质 (ECM) 或邻近细胞产生的机械刺激。将此类物理信号转化为生物反应的细胞内分子过程统称为力转导，对于帮助细胞及时适应微环境的持续动态变化至关重要。 ECM 成分和力学的局部变化是由细胞和基质本身之间的前馈相互作用驱动的，首先沉积的 ECM 蛋白反过来会影响周围的细胞。因此，这些变化在组织发育过程中定期发生，是衰老病理学的标志。然而，直到最近，机械信号在控制细胞功能（例如增殖、分化、迁移）中的重要性才被认识到。在这里，我们通过分析机械刺激如何通过激活特殊的遗传程序转化为给定的生物反应，对细胞机械转导的分子基础的最新见解进行了批判性回顾。具体来说，通过概括细胞-基质间期焦点粘附对 ECM 重塑的解释过程，我们修改了细胞骨架张力作为力转导过程第二信使的作用，以及在阶段和细胞特异性转录因子上聚合的力响应穿梭蛋白的作用。最后，我们给出了一些典型的例子，强调了细胞机械传感装置的故障在病理的发生和进展中的新作用。
Living cells are constantly exposed to mechanical stimuli arising from the surrounding extracellular matrix (ECM) or from neighboring cells. The intracellular molecular processes through which such physical cues are transformed into a biological response are collectively dubbed as mechanotransduction and are of fundamental importance to help the cell timely adapt to the continuous dynamic modifications of the microenvironment. Local changes in ECM composition and mechanics are driven by a feed forward interplay between the cell and the matrix itself, with the first depositing ECM proteins that in turn will impact on the surrounding cells. As such, these changes occur regularly during tissue development and are a hallmark of the pathologies of aging. Only lately, though, the importance of mechanical cues in controlling cell function (e.g., proliferation, differentiation, migration) has been acknowledged. Here we provide a critical review of the recent insights into the molecular basis of cellular mechanotransduction, by analyzing how mechanical stimuli get transformed into a given biological response through the activation of a peculiar genetic program. Specifically, by recapitulating the processes involved in the interpretation of ECM remodeling by Focal Adhesions at cell-matrix interphase, we revise the role of cytoskeleton tension as the second messenger of the mechanotransduction process and the action of mechano-responsive shuttling proteins converging on stage and cell-specific transcription factors. Finally, we give few paradigmatic examples highlighting the emerging role of malfunctions in cell mechanosensing apparatus in the onset and progression of pathologies.
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