Spectroscopic techniques for monitoring protein interactions in living cells

Quantitative protein interaction analysis in living cells remains highly challenging as concentrations of interactions partners are difficult to quantify and to temporally modulate. In this review, the fundamental concepts for monitoring protein interactions in cells are discussed. Next to already well-established resonance energy transfer-based techniques, recent developments of approaches based on single molecule fluctuation and localization are presented. Moreover, the application of surface micropatterning and functionalized nanoparticles for solid phase type of protein interaction analysis in living cells are introduced. The complementary capabilities and limitations of these techniques and future directions based technological developments are discussed.