Taking Care of Bystander FRET in a Crowded Cell Membrane Environment

Abstract

Oligomerization of membrane proteins is a key event in cell signaling, and yet it is challenging to explore experimentally due to the complexity associated with cell membranes (1). The article by King et al. (2) in this issue of the Biophysical Journal describes a strategy for avoiding a major problem in exploring interaction between membrane proteins utilizing fluorescence resonance energy transfer (FRET). The problem has to do with FRET arising from membrane proteins that do not interact, but still give rise to FRET because they happen to be within the required distance for energy transfer (see Fig. 1). This issue assumes relevance in view of the highly crowded nature of the cell membrane (3). FRET from such noninteracting (bystander) pairs complicates the interpretation of FRET results. To our knowledge, King et al. (2) have offered, for the first time, an experimentally verified theoretical framework for membrane proteins, which can be effectively used to correct for bystander FRET.