Penetration of the antimicrobial peptide dicynthaurin into phospholipid monolayers at the liquid-air interface.
This work focuses on the adsorption kinetics of dicynthaurin with lipid monolayers, the effect of peptide adsorption on the structure of the lipid condensed chain lattice, peptide orientation and secondary structure in the adsorbed state. The studies with DPPG as model system revealed strong adsorption and massive incorporation of the peptide into the monolayer. Infrared reflection absorption spectroscopy (IRRAS) experiments showed that the secondary structure of the peptide is maintained upon adsorption. Specular X-ray reflectivity showed the destabilization of the condensed phase of the pure lipid monolayer and revealed a tilted orientation of the long axis of the peptide helix of about 40 degrees from the surface normal. Incorporation of the peptide was found to be pressure dependent, and at high pressure a "squeeze-out" was observed; however, the peptide remained localized to the interface, as suggested by infrared data. These findings were supported by optical fluorescence microscopy measurements which showed the squeeze-out of the peptide on water, but not under physiological conditions. The results suggest that dicynthaurin is able to adsorb to the phosphatidylglycerol-rich inner cytoplasmic membrane of bacteria and alter membrane integrity. To identify and interact with membrane motifs that are characteristic of microbes, but which are absent in eukaryotic cells, might be an intrinsic ability of peptide antibiotics.
Bringezu
Frank
F
Institute of Medical Physics and Biophysics, University of Leipzig, Härtelstrasse 16-18, 04107 Leipzig, Germany. bringezu@denet.de
Majerowicz
Monika
M
Maltseva
Elena
E
Wen
Shaoying
S
Brezesinski
Gerald
G
Waring
Alan J
AJ
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry*; D006461:Hemolysis / Q000187:drug effects; D008567:Membranes, Artificial; D008856:Microscopy, Fluorescence; D008958:Models, Molecular; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D010714:Phosphatidylethanolamines / Q000737:chemistry; D010743:Phospholipids / Q000737:chemistry*; D017433:Protein Structure, Secondary; D013055:Spectrophotometry, Infrared; D014961:X-Ray Diffraction
D000900:Anti-Bacterial Agents; D008567:Membranes, Artificial; D010455:Peptides; D010714:Phosphatidylethanolamines; D010743:Phospholipids; C437228:dicynthaurin; D015060:1,2-Dipalmitoylphosphatidylcholine; C007510:1,2-dipalmitoyl-3-phosphatidylethanolamine