Molecular organization of dengue fusion peptide in phospholipid monolayers revealed by tensiometry and vibrational spectroscopy

The interaction of Dengue fusion peptide (FLAg) (98DRGWGNGCGLFGK110) in selected lipid Langmuir monolayers was characterized by surface pressure-area isotherms and Polarization modulation infrared reflection-absorption spectroscopy (PM-IRRAS) to investigate the role of the membrane charge and molecular organization in the peptide-lipid binding. We aimed to investigate the behavior of FLAg with different lipid compositions using PM-IRRAS to assess the compressional properties of mixed FLAg monolayers as well as molecular information on peptide-lipid interactions. Surface pressure-area isotherms were employed to analyze the thermodynamic and mechanical properties of the FLAg-lipid monolayer, showing that charged lipid monolayers presented different peptide adsorption patterns for a selected peptide concentration. With the peptide, the curves are shifted to higher areas, suggesting its incorporation into the monolayers. When the peptide is incorporated in the lipid monolayers at negligible surface pressures, the isotherms show that the peptide is not expelled from the interface when the monolayer is submitted to compression, even in surface pressure values higher than the exclusion value. Infrared spectroscopy pointed out that incorporating FLAg changed the dipole orientations for the lipid polar head groups, as confirmed in the region around 1100 cm-1 and 1230-70 cm-1 in PG-containing monolayers. Also, FLAg reorients the lipid film when it interacts with the phosphate and choline groups. Our study shows that interactions between the peptide and the lipid should be more pronounced between the peptide region composed of aspartic acid, arginine, asparagine, and lysine residues, and possible hydrogen bonds formed during such interactions, suggesting a region designated to function equally as an “adhesive,” responsible for the virus and cell membrane interactions. Hairpin structures are responsible for the beginning of membrane fusion. Analysis of the 310-helix bands suggests that FLAg assumes a configuration as a hairpin, supposing that the peptide self-arrange at the interface favors the beginning of the fusion process, keeping its biological functions. These results can be associated with this peptide effect on lipidic surfaces, which can be of general relevance for developing pharmaceutical delivery systems.