Role of membrane-tension gated Ca2+ flux in cell mechanosensation
Role of membrane-tension gated Ca2+ flux in cell mechanosensation
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DOI：
10.1242/jcs.208470
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发表时间：
2018-02-01
影响因子：
4
通讯作者：
Sun, Sean X.
中科院分区：
文献类型：
--
作者：
He, Lijuan;Tao, Jiaxiang;Sun, Sean X.
真核细胞对环境中的机械力非常敏感。机械感觉的过程是复杂的，并且涉及诸如细胞骨架和来自肌球蛋白马达的主动收缩的元素。最终，机械感觉与细胞中基因表达的变化有关，称为机械转导。虽然细胞骨架参与机械感觉是已知的，但细胞骨架变化的上游过程尚不清楚。在本文中，通过使用一个微流体装置，机械压缩活细胞，我们表明，钙电流和膜张力敏感的离子通道直接信号的Rho GTdR和肌球蛋白收缩。为了响应膜张力的变化，细胞主动调节皮质肌球蛋白收缩以平衡外力。该过程由机械化学模型捕获，其中膜张力、肌球蛋白收缩以及细胞质和细胞外环境之间的渗透压差通过机械力平衡连接。最后，为了完成机械转导的图片，我们发现，张力敏感的转录因子雅普家族的蛋白质易位从细胞核到细胞质中的机械压缩响应。
Eukaryotic cells are sensitive to mechanical forces they experience from the environment. The process of mechanosensation is complex, and involves elements such as the cytoskeleton and active contraction from myosin motors. Ultimately, mechanosensation is connected to changes in gene expression in the cell, known as mechanotransduction. While the involvement of the cytoskeleton in mechanosensation is known, the processes upstream of cytoskeletal changes are unclear. In this paper, by using a microfluidic device that mechanically compresses live cells, we demonstrate that Ca2+ currents and membrane tension-sensitive ion channels directly signal to the Rho GTPase and myosin contraction. In response to membrane tension changes, cells actively regulate cortical myosin contraction to balance external forces. The process is captured by a mechanochemical model where membrane tension, myosin contraction and the osmotic pressure difference between the cytoplasm and extracellular environment are connected by mechanical force balance. Finally, to complete the picture of mechanotransduction, we find that the tension-sensitive transcription factor YAP family of proteins translocate from the nucleus to the cytoplasm in response to mechanical compression.