title: Composition effect on peptide interaction with lipids and bacteria: variants of C3a peptide CNY21.
abstract: The effect of peptide hydrophobicity and charge on peptide interaction with model lipid bilayers was investigated for the C3a-derived peptide CNY21 by fluorescence spectroscopy, circular dichroism, ellipsometry, z-potential, and photon correlation spectroscopy measurements. For both zwitterionic and anionic liposomes, the membrane-disruptive potency for CNY21 variants increased with increasing net positive charge and mean hydrophobicity and was completely lost on elimination of all peptide positive charges. Analogous effects of elimination of the peptide positive net charge in particular were found regarding bacteria killing for both Pseudomonas aeruginosa and Bacillus subtilis. The peptides, characterized by moderate helix content both in buffer and when attached to the liposomes, displayed high adsorption for the net positively charged peptide variants, whereas adsorption was non-measurable for the uncharged peptide. That electrostatically driven adsorption represents the main driving force for membrane disruption in lipid systems was also demonstrated by a drastic reduction in both liposome leakage and peptide adsorption with increasing ionic strength, and this salt inactivation can be partly avoided by increasing the peptide hydrophobicity. This increased electrolyte resistance translates also to a higher antibacterial effect for the hydrophobically modified variant at high salt concentration. Overall, our findings demonstrate the importance of the peptide adsorption and resulting peptide interfacial density for membrane-disruptive effects of these peptides.
authors.affiliation: Department of Pharmacy, Uppsala University, SE-751 23 Uppsala, Sweden. lovisa.ringstad@farmaci.uu.se
authors.forename: Lovisa
authors.initials: L
authors.lastname: Ringstad
authors.forename: Emma
authors.initials: E
authors.lastname: Andersson Nordahl
authors.forename: Artur
authors.initials: A
authors.lastname: Schmidtchen
authors.forename: Martin
authors.initials: M
authors.lastname: Malmsten
mesh_terms: D000327:Adsorption; D001412:Bacillus subtilis / Q000378:metabolism*; D002942:Circular Dichroism; D015926:Complement C3a / Q000737:chemistry*; D004058:Diffusion; D004573:Electrolytes / Q000737:chemistry; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008051:Lipid Bilayers / Q000737:chemistry; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry; D010455:Peptides / Q000737:chemistry; D017433:Protein Structure, Secondary; D011550:Pseudomonas aeruginosa / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D013499:Surface Properties
chemical_list: D004573:Electrolytes; D008051:Lipid Bilayers; D008055:Lipids; D008081:Liposomes; D010455:Peptides; D015926:Complement C3a; D007770:L-Lactate Dehydrogenase