Effect of peptide length on the interaction between consensus peptides and DOPC/DOPA bilayers.
The effect of peptide length and electrostatics on the interaction between Cardin motif peptides and lipid membranes was investigated for (AKKARA)(n) (n = 1-4) and (ARKAAKKA)(n) (n = 1-3) peptides (A, K, and R refer to alanine, lysine, and arginine, respectively) by fluorescence spectroscopy, circular dichroism, ellipsometry, z potential, and photon correlation spectroscopy measurements. The effect of the peptides regarding leakage induction of both zwitterionic and anionic liposomes increased with increasing peptide length, as did the peptide-induced killing of Enterococcus faecalis and Bacillus subtilis bacteria. The peptides, characterized by a random coil conformation both in buffer and when attached to the liposomes (helix content less than 20%), displayed an increased adsorption with increasing peptide length, and plateau adsorption for the longest peptides corresponded to 1 peptide per 65 and 17 lipid molecules for zwitterionic and anionic membranes, respectively. Control experiments with uncharged peptide analogues as well as experiments at high excess electrolyte concentration showed that peptide charges are important both for peptide adsorption and leakage induction. These observations, together with observations of the liposome z potential at different peptide additions as well as a comparison between the results for zwitterionic and anionic liposomes, suggest that electrostatically affected local packing effects are crucial for the action of these peptides, although pore formation such as that observed for many AMPs cannot be excluded at present.
Ringstad
Lovisa
L
Department of Pharmacy, Uppsala University, P.O. Box 580, SE-751 23 Uppsala, Sweden. lovisa.ringstad@farmaci.uu.se
Schmidtchen
Artur
A
Malmsten
Martin
M
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001412:Bacillus subtilis / Q000187:drug effects; D013293:Enterococcus faecalis; D008051:Lipid Bilayers / Q000737:chemistry*; D008081:Liposomes; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology; D010712:Phosphatidic Acids / Q000737:chemistry*; D010713:Phosphatidylcholines / Q000737:chemistry*; D055672:Static Electricity
D000900:Anti-Bacterial Agents; D008051:Lipid Bilayers; D008081:Liposomes; D010455:Peptides; D010712:Phosphatidic Acids; D010713:Phosphatidylcholines; C050849:1,2-dipalmitoyl glycero-3-thiophosphate; C017251:1,2-oleoylphosphatidylcholine