Effect of Transmembrane Asymmetric Distribution of Lipids and Peptides on Lipid Bilayers

The transbilayer asymmetry of the biomembrane is generated due to the differences in lipid and protein compositions between two leaflets, which plays important roles in physiological functions. However, transbilayer asymmetry can also be originated due to a nonequal number of lipids or proteins in each leaflet, which has not been well recognized. Therefore, to shed light on this field, here we generated theoretical models for the effect of transbilayer asymmetry originated from the differences in the number of lipids and peptides in each leaflet on the state of lipid bilayers. The first model described the effect of asymmetric lipid distribution on the state of lipid bilayers. We obtained theoretical equations for the fractional change in area per lipid in both leaflets as a function of the ratio of the number of lipids in each leaflet, which agreed with the molecular dynamics simulation results quantitatively. Results indicated that tensions in both leaflets are opposite in direction, and their magnitude is the same. We also performed experiments on the effect of lipid insertion in the outer leaflet on the fractional change in area per lipid. These results agreed quantitatively with the values predicted by the above model. The second model described the effect of asymmetric distribution of peptides on the state of lipid bilayers. We obtained theoretical equations for the area per lipid in both leaflets as a function of the surface concentration of peptides located only in the outer leaflet, which agreed with the results of the antimicrobial peptide magainin 2-induced area change.