THE MEMBRANE INTERACTION OF AMPHIPHILIC MODEL PEPTIDES AFFECTS PHOSPHATIDYLSERINE HEADGROUP AND ACYL CHAIN ORDER AND DYNAMICS - APPLICATION OF THE PHOSPHOLIPID HEADGROUP ELECTROMETER CONCEPT TO PHOSPHATIDYLSERINE

Deuterium nuclear magnetic resonance (H-2 NMR) was used to study the interactin of amphiphilic model peptides with model membranes consisting of 1,2-dioleoyl-sn-glycero-3-phospho-L-serine deuterated either at the beta-position of the serine moiety ([2-H-2]DOPS) or at the 11-position of the acyl chains ([11,11-H-2(2)]DOPS). The peptides are derived from the sequences H-Ala-Met-Leu-Trp-Ala-OH (AX, one-letter code with X = MLWA) and H-Arg-Met-Leu-Trp-Ala-OH (RX+) and contain a positive charge of + 1 (AXme+) or + 2 (RXme2+) at the amino terminus or one positive charge at each end of the molecule (AXetN2+). Upon titration of dispersions of DOPS with the peptides, the divalent peptides show a similar extent of binding to the DOPS bilayers, which is larger than that of the single charged peptide. Under these conditions the values of the quadrupolar splitting (DELTA-nu-q) of both [2-H-2]DOPS and [11,11-H-2(2)]DOPS are decreased, indicating that the peptides reduce the order of both the DOPS headgroup and the acyl chains. The extent of the decrease depends on the amount of peptide bound and on the position of the charged moieties in the peptide molecule. The effects exerted by the peptides on the DELTA-nu-q value of [2-H-2]DOPS are consistent with the PS headgroup responding as a molecular electrometer to the surface charge resulting from the presence of the peptides in the lipid-water interface. The effects on the acyl chain deuterons are in agreement with a localization of the peptides intercalated in between the lipid headgroups. Titrations of DOPS with poly(L-lysine)100, which were included for reasons of comparison, reveal increased DELTA-nu-q) values. When the peptide-lipid titrations are carried out without applying a freeze-thaw procedure to achieve full equilibration, two-component H-2 NMR spectra occur. The apparently limited accessibility of the lipid to the peptides under these circumstances is discussed in relation to the ability of the peptides to exhibit transbilayer movement. H-2 spin-lattice relaxation time T1 measurements demonstrate a decrease of the rates of motion of both headgroup and acyl chains of DOPS in the presence of the peptides.