Cell-cell interactions govern basic biological processes, yet there are no practical methods to assess the locations of such interactions in intact organisms. Bioluminescence imaging (with luciferase enzymes and luciferin substrates) is sufficiently sensitive to monitor contacts between cells, but can only approximate cell location in live animals owing to its low spatial resolution. By contrast, cell-cell proximity can be readily detected via static histology sections or intravital microscopy. However, these methods require invasive surgical procedures to collect or expose tissue. We developed a general method for studying cellular interactions in vivo that blends the sensitivity, longitudinal and noninvasive advantages of bioluminescence with the spatial resolution and rich information content of histology. Our strategy relies on the local release of a �caged� nitro-luciferin molecule by �activator� cells (expressing a bacterial nitroreductase, Ntr) and its use by neighboring �reporter� cells (expressing luciferase).  When the cells are in close proximity, robust light emission is observed. We verified that the �caged� luciferin is stable in physiological buffers and can be readily activated via Ntr-mediated reduction to report on cell proximity in vitro. This novel imaging tool will enable the direct visualization of cell-cell interactions relevant to organismal biology and disease.

Visualizing cell-cell interactions with �caged� luciferins

248th National Meeting (2014)

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