Molecular Interactions between Magainin 2 and Model Membranes in Situ

• Published in: The journal of physical chemistry. B Vol. 113; no. 36; pp. 12358 - 12363
• Main Authors: Nguyen, Khoi Tan, Le Clair, Stéphanie V, Ye, Shuji, Chen, Zhan
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 10.09.2009
• Subjects: Animals; Antimicrobial Cationic Peptides - chemistry; B: Biophysical Chemistry; Cell Membrane - chemistry; Magainins; Spectroscopy, Fourier Transform Infrared; Xenopus Proteins - chemistry
• ISSN: 1520-6106; 1520-5207
• DOI: 10.1021/jp904154w

In this paper, we investigated the molecular interactions of magainin 2 with model cell membranes using sum frequency generation (SFG) vibrational spectroscopy and attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR). Symmetric 1-palmitoyl-2-oleoyl-sn-glycero-3-[Phospho-rac-(1-glycerol)] (POPG) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayers, which model the bacterial and mammalian cell membranes, respectively, were used in the studies. It was observed by SFG that magainin 2 orients relatively parallel to the POPG lipid bilayer surface at low solution concentrations, around 200 nM. When increasing the magainin 2 concentration to 800 nM, both SFG and ATR-FTIR results indicate that magainin 2 molecules insert into the POPG bilayer and adopt a transmembrane orientation with an angle of about 20° from the POPG bilayer normal. For the POPC bilayer, even at a much higher peptide concentration of 2.0 μM, no ATR-FTIR signal was detected. For this concentration on POPC, SFG studies indicated that magainin 2 molecules adopt an orientation nearly parallel to the bilayer surface, with an orientation angle of about 75° from the surface normal. This shows that SFG has a much better detection limit than ATR-FTIR and can therefore be applied to study interfacial molecules with a much lower surface coverage. This magainin 2 orientation study and further investigation of the lipid bilayer SFG signals support the proposed toroidal pore model for the antimicrobial activity of magainin 2.