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Haemodynamic and extracellular matrix cues regulate the mechanical phenotype and stiffness of aortic endothelial cells

Caitlin Collins, Lukas D. Osborne, Christophe Guilluy, Zhongming Chen, E. Tim O’Brien, John S. Reader, Keith Burridge, Richard Superfine and Ellie Tzima ()
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Caitlin Collins: University of North Carolina at Chapel Hill
Lukas D. Osborne: University of North Carolina at Chapel Hill
Christophe Guilluy: University of North Carolina at Chapel Hill
Zhongming Chen: University of North Carolina at Chapel Hill
E. Tim O’Brien: University of North Carolina at Chapel Hill
John S. Reader: University of North Carolina at Chapel Hill
Keith Burridge: University of North Carolina at Chapel Hill
Richard Superfine: University of North Carolina at Chapel Hill
Ellie Tzima: University of North Carolina at Chapel Hill

Nature Communications, 2014, vol. 5, issue 1, 1-12

Abstract: Abstract Endothelial cells (ECs) lining blood vessels express many mechanosensors, including platelet endothelial cell adhesion molecule-1 (PECAM-1), that convert mechanical force into biochemical signals. While it is accepted that mechanical stresses and the mechanical properties of ECs regulate vessel health, the relationship between force and biological response remains elusive. Here we show that ECs integrate mechanical forces and extracellular matrix (ECM) cues to modulate their own mechanical properties. We demonstrate that the ECM influences EC response to tension on PECAM-1. ECs adherent on collagen display divergent stiffening and focal adhesion growth compared with ECs on fibronectin. This is because of protein kinase A (PKA)-dependent serine phosphorylation and inactivation of RhoA. PKA signalling regulates focal adhesion dynamics and EC compliance in response to shear stress in vitro and in vivo. Our study identifies an ECM-specific, mechanosensitive signalling pathway that regulates EC compliance and may serve as an atheroprotective mechanism that maintains blood vessel integrity in vivo.

Date: 2014
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4984

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DOI: 10.1038/ncomms4984

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