BME Seminar Series: Keigi Fujiwara

A Molecular Approach to Endothelial Cell Mechanotransduction

Abstract

The ability to respond to various stimuli is a fundamental property of life, and the cells of our body have been shown to react to both chemical and mechanical stimulation. While receptors mediate cells’ response to chemical stimuli or ligands, it is not clear how cells sense mechanical forces. The process by which a cell converts a mechanical force into a biochemical signal is referred to as mechanotransduction. Vascular endothelial cells line the internal surface of the entire cardiovascular system, and as such are exposed to the fluid shear stress of flowing blood. Because the morphology, biosynthesis, gene expression, and pathophysiology of endothelial cells are regulated by shear stress, these cells are used as a model system for studying cellular mechanotransduction. The focus of our research is to identify mechanosensor molecules of the endothelial cell. A number of proteins and cell structures have been suggested to have a mechanosensor function such as ion channels, integrins, glycocalyx, G protein-coupled receptors, and caveolae. We have identified a cell adhesion protein called PECAM-1 (platelet endothelial cell adhesion molecule-1, also called CD31) as a mechanosensor. I will discuss how we identified PECAM-1 as a mechanosensor and present our latest idea on the mechanism of PECAM-1-dependent mechanosignaling. I will also discuss challenges that are unique to mechanosensor research.