Filling gaps in the knowledge of melittin on lipid membranes

Abstract

Melittin (ML) is a small peptide of 26 residues rich in arginine (Arg) and lysine (Lys). Several studies have been done to understand the mechanism of interaction with neutral and negatively charged lipids. However, it is not known with certainty how this interaction depends on the electrostatic or hydrophobic forces according to the composition of the membrane, nor with the different organization of lipids on the membrane, such as the microdomains that could take place in it. Therefore, comparative studies of the interaction and the effect of ML with respect to cationic peptides (Arg-7 and Lys-5) were conducted to get a deeper insight of the ML interaction mechanism with membranes. In this regard, measurements of zeta potential of different model membranes (DOPC, DMPC and DMPE liposomes) in the presence of the peptides, and molecular dynamics simulations were performed. In the special case of DMPC, we worked in its gel like-ripple phase, in order to analyzed defects of packing that potentially expose hydrocarbon regions. In relation with experimental results, molecular analysis of ML interaction with zwiterionic lipid membrane in its ripple phase was performed by unbiased molecular dynamics simulations. The results allow us to remark that ML penetration is favored in the gel-liquid crystalline phase transition in zwitterionic lipids. The importance of this study lies in the understanding of the first stages of action of the ML in eukaryotic membranes, in model systems of its main lipid composition.