Enzyme-Mediated Intercellular Proximity Labeling for Detecting Cell–Cell Interactions

Cell–cell interactions and communications play fundamental roles in life processes but remain largely uncharacterized. We developed an enzyme-mediated proximity cell labeling (EXCELL) strategy as a general method to detect and record cell–cell interactions under living conditions. EXCELL relies on an evolved Staphylococcus aureus transpeptidase sortase A variant (mgSrtA) capable of promiscuous labeling of various cell surface proteins containing a monoglycine residue at the N-terminus. Displaying mgSrtA on the surface of a cell of interest allows the labeling and detection of interacting cells in a proximity-dependent fashion.