The binding of an amphipathic peptide to lipid monolayers at the air/water interface is modulated by the lipid headgroup structure.

We used monolayer techniques combined with infrared reflection absorption spectroscopy (IRRAS) to study the behavior of the 18-mer cationic peptide KLA1 (KLAL KLAL KAW KAAL KLA-NH2) at the air/water interface as well as its interaction with lipid films of different composition. The adsorption of the peptide from the subphase to the air/water interface was observed measuring the increase in surface pressure (π) at constant surface area. The binding of the peptide to lipid monolayers was followed by recording the change in lipid area at a constant surface pressure (π = 30 mN m(-1)). At the air/water interface, the peptide initially adopted an α-helix at large surface area per molecule, that is, low surface pressure, but further accumulation of the peptide at the interface induced a conformational change from α-helix to intermolecular β-sheet, driven by intermolecular aggregation. When the peptide was injected into the subphase underneath lipid monolayers, it adsorbed pronouncedly to anionic monolayers containing phosphatidylglycerol forming an α-helix, but not to zwitterionic lipid monolayers. The large change in area observed upon peptide binding suggests that the peptide helix was incorporated into the apolar chain region of the lipids. An apparent partition coefficient of (0.3-1) × 10(6) M(-1) could be calculated for binding to pure POPG monolayers. Significant differences in binding affinity were observed comparing PG/PC with PG/PE monolayers, with the latter showing a higher binding constant. This shows that not only electrostatic and hydrophobic effects but also specific interactions between the headgroups of the lipids and the peptide side chains modulate the binding affinity.