Detection of peptide-lipid interactions in mixed monolayers, using isotherms, atomic force microscopy, and Fourier transform infrared analyses

To improve the understanding of the membrane uptake of an amphipathic and p ositively charged vector peptide, we studied the interactions of this pepti de with different phospholipids, the nature of whose polar headgroups and p hysical states were varied. Three lipids were considered: dipalmitoylphosph atidylcholine (DPPC), dipalmitoylphosphatidylglycerol (DPPG), and dioleoylp hosphatidylglycerol (DOPG). The approach was carried out by three complemen tary methods: compression isotherms of monolayers and atomic force microsco py observations associated with Fourier transform infrared investigations. From analysis of the compression isotherms, it was concluded that the pepti de interacts with all lipids and with an expansion of the mean molecular ar ea, implying that both components form nonideal mixtures. The expansion was larger in the case of DOPG than for DPPC and DPPG because of an alpha to b eta conformational transition with an increase in the peptide molar fractio n. Atomic force microscopy observations showed that the presence of small a mounts of peptide led to the appearance of bowl-like particles and that an increase in the peptide amounts generated the formation of filaments. In th e case of DOPG, filaments were found at higher peptide molar fractions than already observed for DOPC because of the presence of negatively charged li pid headgroups.