Mechanical Forces in Endothelial Cells during Firm Adhesion and Early Transmigration of Human Monocytes.

Mechanical Forces in Endothelial Cells during Firm Adhesion and Early Transmigration of Human Monocytes.
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DOI:
10.1007/s12195-010-0105-3
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发表时间:
2010-03-01
影响因子:
2.8
通讯作者:
Chen, Christopher S.
Chen, Christopher S.
中科院分区:
工程技术4区
文献类型:
--
作者:
Liu, Zhijun;Sniadecki, Nathan J.;Chen, Christopher S.

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白细胞跨内皮屏障的再迁移是一个严格控制的过程,涉及多个步骤,包括滚动粘附、牢固粘附,然后白细胞穿透内皮单层。虽然我们已经非常详细地描述了关键的分子信号,但我们才刚刚开始揭示这一过程中所涉及的机械力。在这里,使用一个微加工系统,报告细胞产生的牵引力,我们描述单核细胞牢固的粘附和迁移过程中内皮细胞产生的力。当单核细胞牢固粘附和迁移时,穿过内皮单层的平均牵引力显著增加。有趣的是,与单核细胞直接接触的内皮细胞相对于其邻居表现出更大的牵引力,并且这些牵引力的方向相对于单核细胞向心对齐。牵引力的增加发生在单核细胞粘附的局部亚细胞区,并随着距离的增加而迅速消失。为了开始表征这种机械效应的基础,我们表明与单层结合的抗ICAM-1或VCAM-1抗体包被的珠可以再现这种效应。总之,这项研究提供了一种新的方法来检查细胞力学的作用,调节白细胞通过内皮细胞的迁移。
Transmigration of leukocytes across the endothelial barrier is a tightly controlled process involving multiple steps, including rolling adhesion, firm adhesion, and then penetration of leukocytes through the endothelial monolayer. While the key molecular signals have been described in great detail, we are only just beginning to unveil the mechanical forces involved in this process. Here, using a microfabricated system that reports traction forces generated by cells, we describe forces generated by endothelial cells during monocyte firm adhesion and transmigration. Average traction force across the endothelial monolayer increased dramatically when monocytes firmly adhered and transmigrated. Interestingly, the endothelial cell that was in direct contact with the monocyte exhibited much larger traction forces relative to its neighbors, and the direction of these traction forces aligned centripetally with respect to the monocyte. The increase in traction force occurred in the local subcellular zone of monocyte adhesion, and dissipated rapidly with distance. To begin to characterize the basis for this mechanical effect, we show that beads coated with anti-ICAM-1 or VCAM-1 antibodies bound to monolayers could reproduce this effect. Taken together, this study provides a new approach to examining the role of cellular mechanics in regulating leukocyte transmigration through the endothelium.
VCAM-1和ICAM-1与粘附白细胞的新型内皮对接结构中的动态相互作用。
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