This Article Full Text Full Text (PDF) All Versions of this Article: biophysj.106.088161v1 92/1/87    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Ringstad, L. Articles by Malmsten, M. Search for Related Content PubMed PubMed Citation Articles by Ringstad, L. Articles by Malmsten, M.

Composition Effect on Peptide Interaction with Lipids and Bacteria: Variants of C3a Peptide CNY21

Lovisa Ringstad ^*, Emma Andersson Nordahl , Artur Schmidtchen  and Martin Malmsten ^*

^* Department of Pharmacy, Uppsala University, SE-751 23 Uppsala, Sweden; and Department of Dermatology and Venereology, Lund University, Biomedical Center, SE-221 84 Lund, Sweden

Correspondence: Address reprint requests to Lovisa Ringstad, Dept. of Pharmacy, Uppsala University, PO Box 580, SE-751 23 Uppsala, Sweden. E-mail: lovisa.ringstad{at}farmaci.uu.se.

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 nonmeasurable 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.