Non-Uniform Membrane Probe Distribution in Resonance Energy Transfer: Application to Protein–Lipid Selectivity

Biological membranes are, at the molecular level, quasi-two dimensional systems. Membrane components are often distributed non-uniformly in the bilayer plane, as a consequence of lipid phase separation/domain formation or local enrichment/depletion of particular lipid species arising form favorable/unfavorable lipid–membrane protein interactions. Due to its explicit dependence on donor–acceptor distance or local acceptor concentration, resonance energy transfer (RET) has large potential in the characterization of membrane heterogeneity. RET formalisms for the basic geometric arrangements relevant for membranes have now been known for several decades. However, these formalisms usually assume uniform distributions, and more general models are required for the study of membrane lateral heterogeneity. We present a model that addresses the possibility of non-uniform acceptor (e.g., lipid probe) distribution around each donor (e.g., protein) in a membrane. It considers three regions with distinct local acceptor concentration, namely, an exclusion zone, the membrane bulk, and, lying in between, a region of enhanced probability of finding acceptors (annular region). Numerical solutions are presented, and convenient empirical fitting functions are given for RET efficiency as a function of bulk acceptor surface concentration, for several values of the model parameters. The usefulness of the formalism is illustrated in the analysis of experimental data.