Extracellular matrix regulates force transduction at VE-cadherin junctions

Xinyu Kong, Adrian Kapustka, Brendan Sullivan, Gregory J. Schwarz, Deborah E. Leckband

Research output: Contribution to journalArticlepeer-review


Increased tension on VE-cadherin (VE-cad) complexes activates adaptive cell stiffening and local cytoskeletal reinforcement–-two key signatures of intercellular mechanotransduction. Here we demonstrate that tugging on VE-cad receptors initiates a cascade that results in downstream integrin activation. The formation of new integrin adhesions potentiates vinculin and actin recruitment to mechanically reinforce stressed cadherin adhesions. This cascade differs from documented antagonistic effects of integrins on intercellular junctions. We identify focal adhesion kinase, Abl kinase, and RhoA GTPase as key components of the positive feedback loop. Results further show that a consequence of integrin involvement is the sensitization of intercellular force transduction to the extracellular matrix (ECM) not by regulating junctional tension but by altering signal cascades that reinforce cell–cell adhesions. On type 1 collagen or fibronectin substrates, integrin subtypes α2β1 and α5β1, respectively, differentially control actin remodeling at VE-cad adhesions. Specifically, ECM-dependent differences in VE-cad force transduction mirror differences in the rigidity sensing mechanisms of α2β1 and α5β1 integrins. The findings verify the role of integrins in VE-cad force transduction and uncover a previously unappreciated mechanism by which the ECM impacts the mechanical reinforcement of interendothelial junctions.

Original languageEnglish (US)
Article numberar95
JournalMolecular biology of the cell
Issue number11
StatePublished - Sep 15 2022

ASJC Scopus subject areas

  • Medicine(all)


Dive into the research topics of 'Extracellular matrix regulates force transduction at VE-cadherin junctions'. Together they form a unique fingerprint.

Cite this