Lipid Bilayer Perturbations Induced by Simple Hydrophobic Peptides

Abstract

Mixtures of tripeptides of the form Ala-X-Ala-O-tert-butyl with 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) bilayers have been used as a model system for studying the influence of hydrophobic peptides on membrane order and dynamic properties by means of deuterium NMR spectroscopy. Tripeptides with X = Ala, Leu, Phe, and Trp have been examined. Lipid ^2H NMR spectra of acyl chain perdeuteriated DMPC ([^2H_(54))DMPC) show that the addition of peptide disorders the bilayer lipid acyl chains and that the extent of the perturbation increases as the size of the central residue increases. Moment analyses of the spectra indicate that, while the average acyl chain order parameter decreases with increasing central residue size, the order parameter spread across the bilayer (the mean-squared width of the distribution) increases. Lipid segmental ^2H longitudinal relaxation rates, 1/T_1(i), exhibit a square-law functional dependence on S_(CD)(i) both with and without the addition of peptide. The addition of peptide causes an increase in the slope of plots of 1/T_1(i)vs. │S_(CD)(i)│_2 with little change in the 1/T_1(i) intercept, indicating a complex modulation of the acyl chain motions. ^2H NMR spectra of Ala-[^2H_4]Ala-Ala-O-tert-butyl in DMPC bilayers have both isotropic and powder pattern components that vary as a function of temperature. At 30 °C the ^2H spin-lattice relaxation times for the labeled Ala residue increase in going from bilayerincorporated peptide to polycrystalline peptide to polycrystalline Ala·HCI. These experiments provide no information on the location of these peptides in the bilayer. If they protrude into the hydrocarbon core, their disordering influence can be attributed to a direct disruption of acyl chain packing. If they are adsorbed to the bilayer surface, their influence on the bilayer interior must be an indirect disruption propagated via the head group region.