DNA-Directed Activation of Photocatalytic Labeling at Cell–Cell Contact Sites

Cell–cell interactions govern diverse biological activities, necessitating molecular tools for understanding and regulating these interactions. Photoredox chemistry can detect cell–cell interactions by anchoring photocatalysts on cellular membranes to generate reactive species that tag closely contacting cells. However, the activation of photocatalysts lacks precise spatial resolution for selectively labeling intercellular interfaces. Herein, we report a DNA-based approach to selectively activate photocatalytic reactions at cell–cell contacts. Two cell populations are coated with distinct DNA strands, which interact at intercellular contacts, mediating the site-specific turn-on of a Ru(bpy)3-type photocatalyst. We demonstrate high spatial specificity for intercellular chemical labeling in cultured mammalian cells. Furthermore, as a proof of concept, we activate the dynamic DNA catalyst at cell–cell contacts in response to customized DNA triggers. This study lays the foundation for designing versatile chemical tools with high spatial precision and programmable responsiveness, along with the temporal resolution afforded by photoirradiation, to investigate and manipulate cell–cell interactions.