FRET from phase-separated vesicles: An analytical solution for a spherical geometry. 2020

Haden L Scott, and James R Baker, and Aaron J Frederick, and Kristen B Kennison, and Kevin Mendes, and Frederick A Heberle
Center for Environmental Biotechnology, University of Tennessee, Knoxville, TN 37920, United States; Shull Wollan Center, Oak Ridge National Laboratory, Oak Ridge, TN 37831, United States; Department of Chemistry, University of Tennessee, Knoxville, TN 37996, United States.

Förster resonance energy transfer (FRET) is a powerful tool for investigating heterogeneity in lipid bilayers. In model membrane studies, samples are frequently unilamellar vesicles with diameters of 20-200 nm. It is well-known that FRET efficiency is insensitive to vesicle curvature in uniformly mixed lipid bilayers, and consequently theoretical models for FRET typically assume a planar geometry. Here, we use a spherical harmonic expansion of the acceptor surface density to derive an analytical solution for FRET between donor and acceptor molecules distributed on the surface of a sphere. We find excellent agreement between FRET predicted from the model and FRET calculated from corresponding Monte Carlo simulations, thus validating the model. An extension of the model to the case of a non-uniform acceptor surface density (i.e., a phase-separated vesicle) reveals that FRET efficiency depends on vesicle size when acceptors partition between the coexisting phases, and approaches the efficiency of a uniformly mixed bilayer as the vesicle size decreases. We show that this is an indirect effect of constrained domain size, rather than an intrinsic effect of vesicle curvature. Surprisingly, the theoretical predictions were not borne out in experiments: we did not observe a statistically significant change in FRET efficiency in phase-separated vesicles as a function of vesicle size. We discuss factors that likely mask the vesicle size effect in extruded samples.

UI MeSH Term Description Entries
D008051 Lipid Bilayers Layers of lipid molecules which are two molecules thick. Bilayer systems are frequently studied as models of biological membranes. Bilayers, Lipid,Bilayer, Lipid,Lipid Bilayer
D009010 Monte Carlo Method In statistics, a technique for numerically approximating the solution of a mathematical problem by studying the distribution of some random variable, often generated by a computer. The name alludes to the randomness characteristic of the games of chance played at the gambling casinos in Monte Carlo. (From Random House Unabridged Dictionary, 2d ed, 1993) Method, Monte Carlo
D010316 Particle Size Relating to the size of solids. Particle Sizes,Size, Particle,Sizes, Particle
D053835 Unilamellar Liposomes Single membrane vesicles, generally made of PHOSPHOLIPIDS. Monolayer Liposomes,Monolayer Vesicles,Unilamellar Vesicles,Liposomes, Monolayer,Liposomes, Unilamellar,Vesicles, Monolayer,Vesicles, Unilamellar
D056004 Molecular Dynamics Simulation A computer simulation developed to study the motion of molecules over a period of time. Molecular Dynamics Simulations,Molecular Dynamics,Dynamic, Molecular,Dynamics Simulation, Molecular,Dynamics Simulations, Molecular,Dynamics, Molecular,Molecular Dynamic,Simulation, Molecular Dynamics,Simulations, Molecular Dynamics
D031541 Fluorescence Resonance Energy Transfer A type of FLUORESCENCE SPECTROSCOPY using two FLUORESCENT DYES with overlapping emission and absorption spectra, which is used to indicate proximity of labeled molecules. This technique is useful for studying interactions of molecules and PROTEIN FOLDING. Forster Resonance Energy Transfer

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