Molecular details of melittin-induced lysis of phospholipid membranes as revealed by deuterium and phosphorus NMR.

Solid-state deuterium and phosphorus-31 nuclear magnetic resonance (2H and 31P NMR) studies of deuterium-enriched phosphatidylcholine [( 3',3'-2H2]DPPC, [sn-2-2H31]DPPC) and ditetradecylphosphatidylglycerol (DMPG-diether), as water dispersions, were undertaken to investigate the action of melittin on zwitterionic and negatively charged membrane phospholipids. When the lipid-to-protein ratio (Ri) is greater than or equal to 20, the 2H and 31P NMR spectral features indicate that the system is constituted by large bilayer structures of several thousand angstrom curvature radius, at T greater than Tc (Tc, temperature of "gel-to-liquid crystal" phase transition of pure lipid dispersions). At T approximately Tc, a detailed analysis of the lipid chain ordering shows that melittin induces a slight disordering of the "plateau" positions concomitantly with a substantial ordering of positions near the bilayer center. At T much greater than Tc, an apparent general chain disordering is observed. These findings suggest that melittin is in contact with the acyl chain segments and that its position within the bilayer may depend on the temperature. On a cooling down below Tc, for Ri greater than 20, two-phase spectra are observed, i.e., narrow single resonances superimposed on gel-type phosphorus and deuterium powder patterns. These narrow resonances are characteristic of small structures (vesicles, micelles, ... of a few hundred angstrom curvature radius) undergoing fast isotropic reorientation, which averages to zero both the quadrupolar and chemical shift anisotropy interactions. On an increase of the temperature above Tc, the NMR spectra indicate that the system returns reversibly to large bilayer structures.(ABSTRACT TRUNCATED AT 250 WORDS)