Composition effect on peptide interaction with lipids and
bacteria: variants of C3a peptide CNY21
Lovisa Ringstad 1*, Emma Andersson Nordahl 2, Artur Schmidtchen 2 and Martin Malmsten 1
1 Uppsala University
2 Lund University
* To whom correspondence should be addressed. E-mail: lovisa.ringstad{at}farmaci.uu.se.
Submitted on April 28, 2006
Revised on June 19, 2006
Accepted on 28 August 2006
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Abstract |
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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 P. aeruginosa and B. 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, while adsorption was non-measurable for the uncharged peptide. That electrostatically driven adsorption represents the main driving force for membrane disruption in lipid systems was demonstrated also by a drastic reduction in both liposome leakage and peptide adsorption with increasing ionic strength, and that 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.
Key Words:
adsorption, antimicrobial, bilayer, ellipsometry, liposome
