Interaction of an amphipathic peptide with phosphatidycholine/phosphatidylethanolamine mixed membranes

The effect of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) in mixed membranes with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) on interaction with a class A amphipathic peptide, Ac-DWLKAFYDKVAEKLKEAF-NH₂ (Ac-18A-NH₂), was investigated. The fluorescence lifetime of 2-(9-anthroyloxy)stearic acid and ²H NMR spectra were used to evaluate the penetration of water molecules into the membrane interface and the order of lipid acyl chains, respectively. The results demonstrated that DOPE in the mixed membranes decreased the fluorescence lifetime and increased the acyl-chain order, and that Ac-18A-NH₂ affected them more for membranes with higher DOPE fractions. The partition coefficient (K_p) of the peptide to the mixed membranes was increased with the increase in the DOPE mole fractions. From the temperature dependence of the K_p values, the binding of Ac-18A-NH₂ to POPC/DOPE mixed membranes was found to be entropy-driven. The formation of an α-helix at the membrane’s surface is supposed to induce positive curvature strain, which decreases the headgroup hydration and acyl-chain order of lipids. Thus, the binding of Ac-18A-NH₂ to membranes is entropically more favorable at higher DOPE fractions since the peptide’s insertion into the membrane can decrease the order parameter and unfavorable headgroup hydration, which explains the enhanced peptide binding.