Photoactivatable molecular tag illuminates life inside living cells

Osaka, Japan – A novel technology capable of visualizing specific molecules inside living cells using light has been developed by researchers from The University of Osaka and The University of Tokyo. This cutting-edge molecular tagging technique employs a new photo-responsive structure that transforms into a stable terminal alkyne inside cells, enabling precise visualization without disrupting molecular dynamics. The innovation opens a new avenue for understanding how cells and organelles communicate–an insight that could drive future drug discovery.

Scientists have long sought tools to label biomolecules in real time within living cells. Traditional photo-responsive alkyne tags often reacted non-selectively with thiol groups, making intracellular labeling unstable. This challenge called for a more stable and reliable tagging technique for intracellular use.

The team introduced a new chemical structure that transforms into a stable terminal alkyne when exposed to light. When this tag was attached to cholesterol molecules and introduced into cells, only the illuminated regions emitted labeled-fluorescence—allowing precise, light-controlled molecular tracking. With fluorescence visible only in light-exposed areas, the system facilitates the selective visualization of molecules, uncovering previously inaccessible cellular dynamics.

This breakthrough makes it possible to trace molecules at the subcellular level and study “humoral communication” between cells and organelles—offering new insights into biological systems, disease mechanisms, and drug discovery.

“By revisiting decades-old chemical principles, we’ve developed a transformative technology for visualizing molecules inside cells,” said Professor Satoshi Yamaguchi. “This milestone could redefine chemical research directions and biomedical breakthroughs.”

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The article, “Photoactivatable Alkyne Tag for Photolabeling Biomolecules in Living Cells,” was published in ChemBioChem at DOI: https://doi.org/10.1002/cbic.202500190. The concept art was selected for its cover.