Non-Gaussian Diffusion of Individual Lipids Unveils the Unique Peptide-Membrane Interaction Dynamics

The dynamics of protein (or peptide)-membrane interactions plays a central role in cellular functions; however, the underlying mechanisms remain unclear. Herein, through analyzing the diffusion of individual lipids in a bilayer membrane during the membrane actions of typical peptides (e.g., pore-forming peptide melittin and cell-penetrating peptide TAT) at varying concentrations, the spatial heterogeneity as well as temporal dynamics of lipid motions were investigated which showed close correlation with the peptide action mechanism. Specifically, the spatial heterogeneity of lipid diffusion was characterized by the non-Gaussianity of lipid trajectories, which was further decomposed into two basic diffusion modes; moreover, the temporal evolution of the Gaussian fitting parameters provided quantitative information on the varying metastable interaction states between peptides and the membrane (e.g., peptide landing, membrane insertion, and equilibrium). Generally, this work gives an insight into the correlation between single-lipid diffusion and function-realization of membrane-active peptides.