Sellmyer, M.A. et al. Proc. Natl. Acad. Sci. USA 110, 8567–8572 (2013).

If two proteins meet in a cell, chances are that the event can be captured by one of several methods to image protein interactions. But what about detecting two cells that get close in the body? Sellmyer et al. describe a cellular proximity assay based on bioluminescence. Glucose-caged luciferin (Lugal) is fed to cultured cells or to animals, and activator cells expressing β-galactosidase uncage it. The luciferin is then free to diffuse into the surrounding medium, where reporter cells expressing luciferase can take up the luciferin and emit detectable light. Close proximity between activators and reporters leads to brighter luminescence. This assay allowed the researchers to see populations of cells that greet each other in the Petri dish as well as immune cells that associate with breast cancer metastases in the mouse.