Mechanical control of the endothelial barrier
Mechanical control of the endothelial barrier
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DOI：
10.1007/s00441-013-1792-6
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发表时间：
2014-02
影响因子：
3.6
通讯作者：
J. Oldenburg;J. Rooij
中科院分区：
文献类型：
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作者：
J. Oldenburg;J. Rooij
内皮屏障的完整性由化学和机械信号系统的联合作用控制。渗透性调节因子通过小GTP酶发出信号以调节细胞骨架的结构，这对基于VE-钙粘蛋白的细胞-细胞连接的形态和稳定性具有强烈的影响。肌动蛋白细胞骨架的结构和机械特性如何影响细胞-细胞粘附以及这如何影响内皮屏障的动态调节的细节开始被阐明。在这篇综述中，我们讨论了VE-钙粘蛋白复合物和肌动蛋白细胞骨架之间的物理和调节相互作用，因为它们是细胞-细胞粘附和细胞骨架机械结构的主要决定因素。我们讨论，最近在体外数据的基础上，如何平衡之间的线性粘附连接，皮质肌动蛋白束和局灶性粘附连接，连接到径向行动束，决定内皮屏障功能。我们讨论如何小GTP酶控制这种平衡，通过调节肌动球蛋白的空间组织和力学。我们提出了一个假设的模型，生化和机械信号如何合作本地，在肌动球蛋白粘附界面打开和重新密封的障碍，在快速和受控的方式。
The integrity of the endothelial barrier is controlled by the combined action of chemical and mechanical signaling systems. Permeability-regulating factors signal through small GTPases to regulate the architecture of the cytoskeleton and this has a strong impact on the morphology and stability of VE-cadherin-based cell–cell junctions. The details of how structural and mechanical properties of the actin cytoskeleton influence cell–cell adhesion and how this impacts the dynamic regulation of the endothelial barrier, are beginning to be elucidated. In this review, we discuss the physical and regulatory interactions between the VE-cadherin complex and the actomysoin cytoskeleton, as they are the main determinants of cell–cell adhesion and the mechanical architecture of the cytoskeleton. We discuss, based on recent in vitro data, how a balance between Linear Adherens Junctions, paralleled by cortical actin bundles and Focal Adherens Junctions, connected to radial action bundles, determines endothelial barrier function. We discuss how small GTPases control this balance by regulating the spatial organization and mechanics of actomyosin. We propose a hypothetical model of how biochemical and mechanical signals cooperate locally, at the actomyosin–adhesion interface to open and re-seal the barrier in a rapid and controlled manner.