Abstract

In this study, we present results demonstrating that mechanotransduction by vascular endothelial cadherin (VE-cadherin, also known as CDH5) complexes in endothelial cells triggers local cytoskeletal remodeling, and also activates global signals that alter peripheral intercellular junctions and disrupt cell-cell contacts far from the site of force application. Prior studies have documented the impact of actomyosin contractile forces on adherens junction remodeling, but the role of VE-cadherin in force sensation and its ability to influence endothelial cell and tissue mechanics globally have not been demonstrated. Using mechanical manipulation of VE-cadherin bonds and confocal imaging, we demonstrate VE-cadherinbased mechanotransduction. We then demonstrate that it requires homophilic VE-cadherin ligation, an intact actomyosin cytoskeleton, Rho-associated protein kinase 1 (ROCK1) and phosphoinositide 3-kinase. VE-cadherin-mediated mechanotransduction triggered local actin and vinculin recruitment, as well as global signals that altered focal adhesions and disrupted peripheral intercellular junctions. Confocal imaging revealed that VE-cadherin-specific changes appear to propagate across cell junctions to disrupt distant interendothelial junctions. These results demonstrate the central role of VE-cadherin adhesions and the actomyosin cytoskeleton within an integrated, mechanosensitive network that both induces local cytoskeletal remodeling at the site of force application and regulates the global integrity of endothelial tissues.

Original languageEnglish (US)
Pages (from-to)1341-1351
Number of pages11
JournalJournal of cell science
Volume128
Issue number7
DOIs
StatePublished - Jan 1 2015

Fingerprint

Actomyosin
Intercellular Junctions
Cytoskeleton
Endothelium
Endothelial Cells
Vinculin
Adherens Junctions
rho-Associated Kinases
Focal Adhesions
Aptitude
1-Phosphatidylinositol 4-Kinase
cadherin 5
Mechanics
Protein Kinases
Ligation
Actins

Keywords

  • Magnetic twisting cytometry
  • Mechanotransduction
  • VE-cadherin
  • Vinculin

ASJC Scopus subject areas

  • Cell Biology

Cite this

Local VE-cadherin mechanotransduction triggers long-ranged remodeling of endothelial monolayers. / Barry, Adrienne K.; Wang, Ning; Leckband, Deborah E.

In: Journal of cell science, Vol. 128, No. 7, 01.01.2015, p. 1341-1351.

Research output: Contribution to journalArticle

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