Excimer formation of pyrene labeled lipids interpreted by means of coarse-grained molecular dynamics simulations

Abstract

The excimer formation dynamics of pyrene-labeled molecules in lipid bilayers depends on molecular motion over distances of the order of 1-2 nm. From the concentration dependence of the excimer photoemission curve, it is possible to derive a value for the lipid self-diffusion coefficient. This technique has been intensively used in the past twenty years, leading to rather large numerical values for self-diffusion compared with other approaches based on fluorescent probes tracking. In most cases, the interpretation of the experimental data rely on models for diffusion limited 2d reaction rates, or comparison with 2d lattice random walks. Our approach uses realistic molecular dynamics trajectories to reinterpret these experiments. Based on a well established coarse-grained model for lipid MD simulations (Martini), we show how to relate simulation results to experimental data on excimer formation. Our procedure is quite general and is applicable to all diffusion-limited kinetic processes. Key to our approach is the determination of the acceleration factor of lipid coarse-grained numerical models compared to reality. We find a significant reduction of the diffusion coefficient values, in particular when interleaflet association is taken into account. Our work does not point to deviation from a diffusion-limited mechanism but indicates that the excimer formation across bilayer leaflets could be hindered.