Actin stress fibers transmit and focus force to activate mechanosensitive channels
Actin stress fibers transmit and focus force to activate mechanosensitive channels
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DOI：
10.1242/jcs.022053
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发表时间：
2008-02-15
影响因子：
4
通讯作者：
Sokabe, Masahiro
中科院分区：
文献类型：
--
作者：
Hayakawa, Kimihide;Tatsumi, Hitoshi;Sokabe, Masahiro
机械敏感(MS)通道在从细菌到人类的广泛系统发育谱系中的各种细胞中表达。了解其激活的分子和生物物理机制是一个重要的研究方向。真核生物的MS通道是否需要辅助蛋白--通常是细胞骨架结构--来激活是有争议的，因为MS通道的活动是由影响细胞骨架的药物治疗来调节的。在这里，我们证明了使用光钳对肌动蛋白应激纤维进行直接机械刺激(拉伸)可以激活培养的人脐静脉内皮细胞(HUVECs)的MS通道。此外，利用高速全内反射显微镜，我们显示了分布在HUVECs基底面焦点粘连附近的单个MS通道中钙离子内流的斑点。本研究首次提供了细胞骨架作为一种力传递和力聚焦的分子装置来激活真核细胞中的MS通道的直接证据。
Mechanosensitive (MS) channels are expressed in various cells in a wide range of phylogenetic lineages from bacteria to humans. Understanding the molecular and biophysical mechanisms of their activation is an important research pursuit. It is controversial whether eukaryotic MS channels need accessory proteins-typically cytoskeletal structures - for activation, because MS channel activities are modulated by pharmacological treatments that affect the cytoskeleton. Here we demonstrate that direct mechanical stimulation (stretching) of an actin stress fiber using optical tweezers can activate MS channels in cultured human umbilical vein endothelial cells (HUVECs). Furthermore, by using high-speed total internal reflection microscopy, we visualized spots of Ca2+ influx across individual MS channels distributed near focal adhesions in the basal surface of HUVECs. This study provides the first direct evidence that the cytoskeleton works as a force-transmitting and force-focusing molecular device to activate MS channels in eukaryotic cells.