Morphological Responses of Vascular Endothelial Cells Induced by Local Stretch Transmitted Through Intercellular Junctions

Abstract

It has been well established that mechanical stimuli including fluid shear stress and cyclic stretch play a key role in endothelial cell (EC) remodeling. However, in contrast to global remodeling to these mechanical stimuli, little is known of how local mechanical forces are transmitted through cells to induce cell remodeling leading to alteration in cell functions. In this study, we demonstrated that EC remodeling can be exerted by local tension generated in a neighboring EC. In this technique, a glass microneedle was used to apply local stretch in an EC in confluent monolayer and the resulting tension is transmitted to a neighboring EC across intercellular junctions. Local stretch induced reorientation and elongation of ECs parallel to the direction of stretch associated with reorganization of stress fibers. In addition, recruitment of Src homology 2-containing tyrosine phosphatase-2, binding to intercellular adhesion molecules platelet-endothelial cellular adhesion molecules-1, was selectively observed at the force-transmitted intercellular junctions after application of local stretch. These findings suggest that intercellular junctions can not only transmit but also sense local forces, and are potentially involved in EC mechanotransduction pathways.