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Standardized and Scalable Assay to Study Perfused 3D Angiogenic Sprouting of iPSC-derived Endothelial Cells In Vitro

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OptoBarrier: An Optogenetic Platform for Modulating Endothelial Barriers In Vitro.

Sharon Fleischer¹, Martin Liberman¹, Max Summers¹

¹Department of Biomedical Engineering, Columbia University, New York, New York 10032, United States.

ACS Biomaterials Science & Engineering

|August 14, 2025

Summary

This summary is machine-generated.

Optogenetic organ-on-a-chip technology, optoBarrier, uses light to control endothelial barrier permeability. This novel platform enables precise, reversible modulation of vascular function for advanced drug screening and disease modeling.

Keywords:

engineered vasculature in vitro modeling optogenetics organ-on-a-chip vascular permeability

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Area of Science:

Biotechnology
Cell Biology
Vascular Biology

Background:

Organ-on-a-chip platforms are advanced in vitro models for drug screening.
Vascular integration is crucial for organoid fidelity and interorgan studies.
Current models lack control over organ-specific endothelial permeability.

Purpose of the Study:

To develop an optogenetic platform, optoBarrier, for light-controlled modulation of endothelial barrier permeability.
To investigate the impact of optical stimulation on endothelial cell signaling and barrier function.
To provide a tunable and reversible method for manipulating vascular permeability in vitro.

Main Methods:

Engineered optogenetic endothelial cells were integrated into an organ-on-a-chip system.
Light stimulation was used to optically activate RhoA signaling pathways.
Endothelial barrier integrity and permeability were assessed via stress fiber formation, VE-cadherin disruption, and permeability assays.

Main Results:

OptoBarrier successfully modulated endothelial barrier permeability using light.
Optical activation induced stress fiber formation and disrupted VE-cadherin.
Permeability changes were reversible and dose-dependent on light exposure.

Conclusions:

OptoBarrier provides a user-defined, controlled method for manipulating endothelial permeability.
This platform facilitates in vitro studies of human vasculature and disease mechanisms.
OptoBarrier advances organ-on-a-chip technology for drug discovery and physiological research.