A “Caged” Luciferin for Imaging Cell–Cell Contacts

Cell–cell interactions underlie fundamental biological processes but remain difficult to visualize over long times and large distances in tissues and live organisms. Bioluminescence imaging with luciferase–luciferin pairs is sufficiently sensitive to image cells in vivo but lacks the spatial resolution to identify cellular locations and interactions. To repurpose this technology for visualizing cellular networks, we developed a "caged" luciferin that produces light only when cells are in close contact. This molecule comprises a nitroaromatic core that can be selectively reduced ("uncaged") by one cell type, liberating a luciferin that can be selectively consumed by neighboring, luciferase-expressing cells. When the two cell types are in contact, robust light emission is observed. This imaging strategy will enable the noninvasive visualization of cell–cell interactions relevant to organismal biology.