The effect of peptide/lipid hydrophobic mismatch on the phase behavior of model membranes mimicking the lipid composition in Escherichia coli membranes

The effect of hydrophobic peptides on the lipid phase behavior of an aqueou s dispersion of dioleoylphosphatidylethanolamine and dioleoylphosphatidylgl ycerol (7:3 molar ratio) was studied by P-31 NMR spectroscopy The peptides (WALPn peptides, where n is the total number of amino acid residues) are de signed as models for transmembrane parts of integral membrane proteins and consist of a hydrophobic sequence of alternating leucines and alanines, of variable length, that is flanked on both ends by tryptophans. The pure lipi d dispersion was shown to undergo a lamellar-to-isotropic phase transition at similar to 60 degrees C. Small-angle x-ray scattering showed that a? a l ower water content a cubic phase belonging to the space group Pn3m is forme d, suggesting also that the isotropic phase in the lipid dispersion represe nts a cubic liquid crystalline phase. It was found that the WALP peptides v ery efficiently promote formation of nonlamellar phases in this lipid syste m. At a peptide-to-lipid (P/L) molar ratio of 1:1000, the shortest peptide used, WALP16, lowered the lamellar-to-isotropic phase transition by similar to 15 degrees C. This effect was less for longer peptides. For all of the WALP peptides used, an increase in peptide concentration led to a further l owering of the phase transition temperature. At the highest P/L ratio (1:25 ) studied, WALP16 induced a reversed hexagonal liquid crystalline (H-II) ph ase, while the longer peptides still promoted the formation of an isotropic phase. Peptides with a hydrophobic length larger than the bilayer thicknes s were found to be unable to inhibit formation of the isotropic phase. The results are discussed in terms of mismatch between the hydrophobic length o f the peptide and the hydrophobic thickness of the lipid bilayer and its co nsequences for lipid-protein interactions in membranes.