OptoBarrier: An Optogenetic Platform for Modulating Endothelial Barriers In Vitro

Organ-on-a-chip platforms have emerged as promising human tissue models for drug screening and mechanistic studies, offering alternatives to traditional animal models. Integration of vascular structures into these platforms is pivotal for creating physiologically faithful models of individual organs and studying interorgan crosstalk. However, most vascular structures grown in vitro do not account for organ-specific endothelial permeability or its modulation in response to disease. Here, we present optoBarrier, an optogenetic organ-on-a-chip platform designed to modulate endothelial barrier permeability through light stimulation. By optically activating RhoA signaling in engineered optogenetic endothelial cells, we demonstrate the formation of stress fibers, disruption of vascular endothelial cadherin (VE-cadherin) and increased barrier permeability. We further show that permeability is tunable in a reversible and dose-dependent manner in response to light. We therefore propose that optoBarrier offers a user-defined, controlled and simple method to manipulate endothelial permeability for in vitro studies of human vasculature.