Peripheral adsorption of polylysine on one leaflet of a lipid bilayer reduces the lipid diffusion of both leaflets

Understanding polycation-lipid interaction is essential not only in molecular biology but also in the biomedical industry and pharmacology. However, the effect of the polycation-lipid interaction on the molecular properties of lipids in biomembranes remains elusive. Here, two fluorescence correlation spectroscopies (FCSs), pulse-interleaved excitation (PIE) FCS and lifetime-based FCS, were performed to elucidate the change in the lipid diffusion of a model biomembrane induced by polylysine (PLL) adsorption. The results of PIE-FCS showed that the diffusions of both anionic and zwitterionic lipids become slower in the presence of PLL but the mobility of the anionic lipids is much reduced, suggesting the preferential interaction between the PLL and the anionic lipids due to the electrostatic attraction. Furthermore, leaflet-specific lipid diffusion analysis by lifetime-based FCS clearly showed that PLL adsorption on one leaflet of the membrane reduces the lipid diffusion of both leaflets in the same manner. This clearly indicates that the interleaflet coupling is strong in the presence of PLL. Leaflet-specific lipid diffusion analysis revealed that polylysine adsorption on one leaflet of a lipid bilayer is sensed by the opposite leaflet.