β1 integrin is a sensor of blood flow direction

• DOI: 10.1242/jcs.229542
• Publication Date: 2019-05-10T14:35:23Z
• Authors: Ioannis Xanthis; Celine Souilhol; Jovana Serbanovic...; Hannah Roddie; Antreas C. Kalli; Maria Fragiadaki; Raymond Wong; Dhruv R. Shah; Janet A. Askari; Lindsay Canham; Nasreen Akhtar; Shuang Feng; Victoria Ridger; Jonathan Waltho; Emmanuel Pinteaux; Martin J. Humphries; Matthew T. Bryan; Paul C. Evans
• Keywords: Mice, Knockout; 0301 basic medicine; 0303 health sciences; Integrin beta1; Cell Line; Mice; 03 medical and health sciences; Regional Blood Flow; Stress, Physiological; Human Umbilical Vein Endothelial Cells; Animals; Humans; Female; Mechanoreceptors; Aorta; Research Article

ABSTRACT 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.