Shear Stress Modulates Endothelial Ca2+ Signaling and Barrier Integrity in a Microfluidic Organ-on-a-Chip Platform

Endothelial cells (ECs) line the blood vessels and form the primary barrier between the bloodstream and the brain. Blood flow exerts a modulatory effect on the endothelial phenotype, and evidence indicates that capillary-like fluid shear stress enhances endothelial tight junctions and transporters. ECs possess mechanosensitive channels that activate endothelial responses and modulate their functions. Among the various responses to shear stress, morphological adaptations have been the most extensively studied, while functional live responses remain mostly unexplored. Calcium has been identified as key modulators that translates mechanical stimuli into biological processes, regulating endothelial activity. In this study we investigate the effect of acute and long-term shear stress on endothelial cells through live calcium imaging and immunocytochemistry, by using a modular 3D printed organ-on-a-chip, capable of simulating in-vivo capillary and enabling the possibility to study cellular crosstalk.