Substrate stiffness and VE-cadherin mechano-transduction coordinate to regulate endothelial monolayer integrity.
Substrate stiffness and VE-cadherin mechano-transduction coordinate to regulate endothelial monolayer integrity.
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DOI：
10.1016/j.biomaterials.2017.06.010
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发表时间：
2017-09
期刊：
影响因子：
14
通讯作者：
Leckband DE
中科院分区：
文献类型：
--
作者：
Andresen Eguiluz RC;Kaylan KB;Underhill GH;Leckband DE
血管内皮受到调节血管内皮屏障功能的多种机械信号的影响。除了通过整合素粘附进行刚性传感外，机械扰动（例如流体剪切应力的变化）也可以激活细胞间连接处的力传导信号。本研究研究了血管内皮钙粘蛋白激活的细胞外基质刚性和细胞间力传导如何协调调节内皮单层的完整性。研究使用了对在不同刚度的图案化基底上生长的内皮单层进行补充机械测量。特别扰乱 VE-钙粘蛋白受体会激活细胞间力传导信号，从而增加整合素依赖性细胞收缩性并破坏细胞与细胞和细胞与基质的粘附。进一步研究基质刚性对力转导信号的影响，证明细胞如何整合细胞外力学线索和细胞间力转导信号，以调节内皮完整性和整体组织力学。 VE-钙粘蛋白特异性信号传导增加粘着斑重塑和细胞收缩性，同时维持中尺度的整体机械平衡。相反，增加的基质刚性会增加单层应力分布的不均匀性，从而加剧细胞间力传导的破坏作用。这些结果为基质硬度和细胞间力传导如何协调调节内皮单层完整性提供了新的见解。
The vascular endothelium is subject to diverse mechanical cues that regulate vascular endothelial barrier function. In addition to rigidity sensing through integrin adhesions, mechanical perturbations such as changes in fluid shear stress can also activate force transduction signals at intercellular junctions. This study investigated how extracellular matrix rigidity and intercellular force transduction, activated by vascular endothelial cadherin, coordinate to regulate the integrity of endothelial monolayers. Studies used complementary mechanical measurements of endothelial monolayers grown on patterned substrates of variable stiffness. Specifically perturbing VE-cadherin receptors activated intercellular force transduction signals that increased integrin-dependent cell contractility and disrupted cell-cell and cell-matrix adhesions. Further investigations of the impact of substrate rigidity on force transduction signaling, demonstrated how cells integrate extracellular mechanics cues and intercellular force transduction signals, to regulate endothelial integrity and global tissue mechanics. VE-cadherin specific signaling increased focal adhesion remodeling and cell contractility, while sustaining the overall mechanical equilibrium at the mesoscale. Conversely, increased substrate rigidity exacerbates the disruptive effects of intercellular force transduction, by increasing heterogeneity in monolayer stress distributions. The results provide new insights into how substrate stiffness and intercellular force transduction coordinate to regulate endothelial monolayer integrity.
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影响因子：
3.1
作者：
Birukova, Anna A.;Tian, Xinyong;Cokic, Ivan;Beckham, Yvonne;Gardel, Margaret L.;Birukov, Konstantin G.
通讯作者：
Birukov, Konstantin G.
影响因子：
2.9
作者：
Amano, Mutsuki;Nakayama, Masanori;Kaibuchi, Kozo
通讯作者：
Kaibuchi, Kozo
DOI：
10.1083/jcb.201408103
发表时间：
2015-03-30
期刊：
The Journal of cell biology
影响因子：
--
作者：
Coon BG;Baeyens N;Han J;Budatha M;Ross TD;Fang JS;Yun S;Thomas JL;Schwartz MA
通讯作者：
Schwartz MA
影响因子：
8.3
作者：
Chien, S;Li, S;Shyy, JYJ
通讯作者：
Shyy, JYJ
影响因子：
14.8
作者：
Brafman, David A.;Chien, Shu;Willert, Karl
通讯作者：
Willert, Karl