Membrane potential depolarization decreases the stiffness of vascular endothelial cells
Membrane potential depolarization decreases the stiffness of vascular endothelial cells
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DOI：
10.1242/jcs.084657
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发表时间：
2011-06-01
影响因子：
4
通讯作者：
Oberleithner, Hans
中科院分区：
文献类型：
--
作者：
Callies, Chiara;Fels, Johannes;Oberleithner, Hans
血管内皮细胞的硬度对于机械承受血流并同时控制变形依赖性一氧化氮的释放至关重要。然而，机械刚度的调节尚不清楚。有证据表明，可能的调节器是质膜电势差。本研究使用一种将基于荧光的膜电位记录与基于原子力显微镜 (AFM) 的刚度测量相结合的新技术，表明膜去极化与内皮细胞刚度的降低有关。应用三种不同的去极化方案，所有这些都导致细胞硬度类似且显着的降低，与细胞体积的变化无关。此外，使用肌动蛋白不稳定剂细胞松弛素 D 进行的实验表明，去极化是通过影响皮质肌动蛋白细胞骨架来发挥作用的。提出了一种模型，通过膜下肌动蛋白网络直接感知跨质膜的电场变化，调节肌动蛋白聚合：解聚比率，从而调节细胞刚度。这种去极化引起的内皮细胞硬度降低可能在血流介导的一氧化氮依赖性血管舒张中发挥作用。
The stiffness of vascular endothelial cells is crucial to mechanically withstand blood flow and, at the same time, to control deformation-dependent nitric oxide release. However, the regulation of mechanical stiffness is not yet understood. There is evidence that a possible regulator is the electrical plasma membrane potential difference. Using a novel technique that combines fluorescence-based membrane potential recordings with atomic force microscopy (AFM)-based stiffness measurements, the present study shows that membrane depolarization is associated with a decrease in the stiffness of endothelial cells. Three different depolarization protocols were applied, all of which led to a similar and significant decrease in cell stiffness, independently of changes in cell volume. Moreover, experiments using the actin-destabilizing agent cytochalasin D indicated that depolarization acts by affecting the cortical actin cytoskeleton. A model is proposed whereby a change of the electrical field across the plasma membrane is directly sensed by the submembranous actin network, regulating the actin polymerization: depolymerization ratio and thus cell stiffness. This depolarization-induced decrease in the stiffness of endothelial cells could play a role in flow-mediated nitric-oxide-dependent vasodilation.