Journal Article

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

Guilluy, Christophe, Superfine, Richard, Reader, John S., Collins, Caitlin, Osborne, Lukas D., Chen, Zhongming, O’Brien, E. Tim, Burridge, Keith, Tzima, Ellie

2014

Overview

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 . Endothelial cells at the inner surface of blood vessels are exposed to mechanical forces as a result of blood flow. Here the authors show that the interaction of extracellular matrix proteins with adhesion molecules on the endothelial cell surface determines cellular stiffness and sensitivity to mechanical forces.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 13/1 / 13/95 / 14/19 / 14/63 / 631/443/592/75/593/2724 / 631/80/79/2066 / 631/80/86 / 64/60 / 82/1 / 82/29 / 96/63 / 96/95 / Adhesion / Animals / Aorta - cytology / Aorta - enzymology / Aorta - metabolism / Aorta - physiology / Cyclic AMP-Dependent Protein Kinases - metabolism / Endothelium, Vascular - cytology / Endothelium, Vascular - enzymology / Endothelium, Vascular - metabolism / Endothelium, Vascular - physiology / Extracellular Matrix - enzymology / Extracellular Matrix - metabolism / Extracellular Matrix - physiology / Focal Adhesions / Hemodynamics / Humanities and Social Sciences / Inactivation / Male / Mice / Mice, Inbred C57BL / multidisciplinary / Platelet Endothelial Cell Adhesion Molecule-1 - metabolism / rhoA GTP-Binding Protein - metabolism / Science / Science (multidisciplinary) / Shear stress