Understanding the molecular mechanisms of protein–protein interactions at the cell surface of living cells is fundamental to identifying the nature of cellular processes. Here, we discuss how fluorescence-based approaches have been successfully developed to visualize protein–protein interactions in living cells. F�rster resonance energy transfer (FRET) is unique in generating fluorescence signals between proteins that are highly spatially sensitive. Furthermore, total internal reflectance fluorescence (TIRF) microscopy combined with FRET is a robust technique used to assay protein/protein interactions and the functionality of proteins assembled at the cell surface membrane.
