HKUST Engineers Develop CarGAP, a Vitamin B₁₂ and Light-Controlled Molecular Valve to Precisely Regulate Cell Communication
Researchers at The Hong Kong University of Science and Technology (HKUST) have developed CarGAP, a groundbreaking chemo-optogenetic tool that uses vitamin B₁₂ and green light to precisely control gap junctions, the microscopic channels enabling direct cell-to-cell communication. This innovation allows on-demand closing and opening of these intercellular bridges, providing unprecedented spatiotemporal control over vital molecules and electrical signals. Demonstrated in both mammalian cells and living fruit flies, CarGAP provides a powerful new way to study development, immunity, and neural activity, with far-reaching potential for understanding disease mechanisms and advancing regenerative medicine.
Gap junctions are essential for life, acting as direct conduits for ions, second messengers, and small molecules that coordinate cellular activities ranging from heartbeats to brain function. When these channels malfunction, they can contribute to cardiovascular disease, developmental disorders, and even cancer. However, studying their precise roles has been challenging. Traditional methods such as gene knockouts are permanent and blunt, while chemical inhibitors are often non-specific and may be toxic. A tool that can turn gap junctions on and off like a switch—with high precision and minimal side effects—has long been a major unmet need in cell biology and neurobiology.
The central challenge was creating a method to control gap junctions that was both reversible and biocompatible, without disrupting the cell’s natural processes. Existing optogenetic tools often rely on blue light, which can be toxic over time, while chemical approaches lack spatial precision. The team needed a system that could be genetically encoded, respond to a harmless stimulus, and work across different species—from human cells to complex model organisms like fruit flies.
The HKUST team, led by Prof. SUN Fei, Professor of the Department of Chemical and Biological Engineering; Prof. XIE Ting, Kerry Holdings Professor of Science and Chair Professor of the Division of Life Science; and Dr. TU Renjun, former Research Assistant Professor of the Division of Life Science (now Professor of Southeast University in Nanjing), collaborated with Prof. ZOU Peng from the College of Chemistry and Molecular Engineering at Peking University, to develop CarGAP by fusing gap junction proteins (connexins in vertebrates, innexins in invertebrates) with a light-sensitive vitamin B₁₂-binding domain from a bacterial protein called CarHC. In the dark, adding vitamin B₁₂ (AdoB12) causes the CarHC domains to oligomerize, physically blocking the channel. Shining a gentle green light (570 nm) triggers the disassembly of these protein blocks, reopening the channel. This elegant design allows researchers to close gap junctions with a simple vitamin and reopen them with a flash of light.
The team validated CarGAP in multiple contexts: they controlled the transfer of a fluorescent dye and the immune-signaling molecule 2′3′-cGAMP between mammalian cells, and used a far-red voltage sensor, NAVI-Cy5, to optically record the restoration of electrical coupling between cells after light exposure. Most impressively, they introduced CarGAP into the ovaries of living fruit flies, where they were able to block and then restore the flow of the key signaling molecule cAMP between stem cells and their supporting niche cells, thereby directly influencing stem cell behavior and egg development.
“CarGAP gives us a remote-control interface for one of the most fundamental forms of cellular communication,” said Prof. Sun, co-corresponding author of the study. “By combining the biocompatibility of vitamin B₁₂ with the precision of light control, we can now ask questions about how cells coordinate their behavior in real time—whether in an embryo, a brain, or a tumor. This tool opens a new window into the dynamic language of cells.”
The research findings were published in the Proceedings of the National Academy of Sciences (PNAS) in a paper titled “Controllable gap junctions by vitamin B₁₂ and light”. The three co-first authors of the study are CUI Duo and HUANG Xinyu, both HKUST PhD students in Prof. Sun’s group, and Dr. LIU Shuzhang, postdoctoral fellow of Peking University.
About The Hong Kong University of Science and Technology
The Hong Kong University of Science and Technology (HKUST) (https://hkust.edu.hk/) is a world-class university known for its innovative education, research excellence, and impactful knowledge transfer. With a holistic and interdisciplinary pedagogy approach, HKUST was ranked 6th in the QS Asia University Rankings 2026, 3rd in the Times Higher Education’s Young University Rankings 2024, and 19th globally and 1st in Hong Kong in the Times Higher Education’s Impact Rankings 2025. Thirteen HKUST subjects were ranked among the world’s top 50 in the QS World University Rankings by Subject 2025, with “Data Science and Artificial Intelligence” coming in 17th worldwide and first in Hong Kong. Our graduates are highly competitive, consistently ranking among the world’s top 30 most sought-after employees. In terms of research and entrepreneurship, over 80% of our work was rated “internationally excellent” or “world leading” in the Research Assessment Exercise 2020 of the Hong Kong’s University Grants Committee. As of January 2026, HKUST members have founded over 1,900 active start-ups, including 10 Unicorns and 21 exits (IPO or M&A).
(This news was originally published by the HKUST Global Engagement and Communications Office here.)
