Open Accessβ1 integrin is a sensor of blood flow direction
Author(s) -
Ioannis Xanthis,
Céline Souilhol,
Jovana Serbanovic-Canic,
Hannah Roddie,
Antreas C. Kalli,
Maria Fragiadaki,
Raymond Wong,
Dhruv R Shah,
Janet A. Askari,
Lindsay Canham,
Nasreen Akhtar,
Shuang Feng,
Victoria Ridger,
Jonathan P. Waltho,
Emmanuel Pinteaux,
Martin J. Humphries,
Matthew T. Bryan,
Paul C. Evans
Publication year - 2019
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.229542
Subject(s) - integrin , biology , microbiology and biotechnology , blood flow , shear stress , biophysics , cell , mechanics , biochemistry , physics , medicine
Endothelial cell (EC) sensing of fluid shear stress direction is a critical determinant of vascular health and disease. Unidirectional flow induces EC alignment and vascular homeostasis, whereas bidirectional flow has pathophysiological effects. ECs express several mechanoreceptors that respond to flow, but the mechanism for sensing shear stress direction is poorly understood. We determined, by using in vitro flow systems and magnetic tweezers, that β1 integrin is a key sensor of force direction because it is activated by unidirectional, but not bidirectional, shearing forces. β1 integrin activation by unidirectional force was amplified in ECs that were pre-sheared in the same direction, indicating that alignment and β1 integrin activity has a feedforward interaction, which is a hallmark of system stability. En face staining and EC-specific genetic deletion studies in the murine aorta revealed that β1 integrin is activated and is essential for EC alignment at sites of unidirectional flow but is not activated at sites of bidirectional flow. In summary, β1 integrin sensing of unidirectional force is a key mechanism for decoding blood flow mechanics to promote vascular homeostasis.This article has an associated First Person interview with the first author of the paper.