Interactions of Two Fragments of the Human Antimicrobial Peptide LL-37 with Zwitterionic and Anionic Lipid Monolayers

The interactions of two fragments of the human antimicrobial LL-37 (LL-32 and LL-20) with lipid monolayers at the soft liquid/air interface have been characterized. To model the interaction with mammalian cell membranes, lipid monolayers composed of the zwitterionic DPPC and DOPC were used. To investigate the interaction with bacterial cell membranes, lipid monolayers of anionic DPPG and POPG were used. DPPC and DPPG exhibit a first-order phase transition from the disordered liquid to the ordered condensed state, whereas POPG and DOPC monolayers are in the fluid disordered state at all surface pressures studied. Therefore, the influence of the monolayer phase state on peptide-lipid interactions can be studied. To obtain insight into the peptide structure and their influence on phospholipid membranes, film balance measurements were coupled with surface sensitive Infrared Reflection-Absorption Spectroscopy (IRRAS). The results were compared to CD measurements in bulk. LL-32 is more surface active and can better intercalate into lipid monolayers than LL-20. Even though LL-32 has no cell-selectivity, our results show how the peptide interacts differently with zwitterionic compared to anionic membrane models. The interaction with DPPC monolayers is based on simple intercalation of the peptides between the lipid molecules. However, the peptides bind in a two-step process to DPPG monolayers, which results in a fluidization of the lipid film. This can be related to a membrane thinning.