Abstract
Cell-to-cell communications are critical to biological processes ranging from embryonic development to cancer progression. Several imaging strategies have been developed to capture such interactions, but many are challenging to deploy in thick tissues and other complex environments. Here, we report a platform termed Luminescence to Observe and Track Intercellular Interactions (LOTIIS). The approach features split fragments of a luciferase enzyme that reassemble when target cells come into proximity. One fragment is secreted by "sender" cells, and the complementary piece is secreted by "receiver" cells. Split reporter assembly is facilitated by a single chain variable fragment (scFv)-peptide interaction on the receiver cell, resulting in localized light production. We demonstrate that LOTIIS can rapidly label cells in close proximity in a time- and distance-dependent fashion. The platform is also compatible with bioluminescence resonance energy transfer probes for multiplexed imaging. Collectively, these data suggest that LOTIIS will enable a variety of cellular interactions to be tracked in biological settings.