Abstract
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. Förster 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.