Effect of lipid headgroup composition on the interaction between melittin and lipid bilayers.
The effect of the lipid polar headgroup on melittin-phospholipid interaction was investigated by cryo-TEM, fluorescence spectroscopy, ellipsometry, circular dichroism, electrophoresis and photon correlation spectroscopy. In particular, focus was placed on the effect of the lipid polar headgroup on peptide adsorption to, and penetration into, the lipid bilayer, as well as on resulting colloidal stability effects for large unilamellar liposomes. The effect of phospholipid headgroup properties on melittin-bilayer interaction was addressed by comparing liposomes containing phosphatidylcholine, -acid, and -inositol at varying ionic strength. Increasing the bilayer negative charge leads to an increased liposome tolerance toward melittin which is due to an electrostatic arrest of melittin at the membrane interface. Balancing the electrostatic attraction between the melittin positive charges and the phospholipid negative charges through a hydration repulsion, caused by inositol, reduced this surface arrest and increased liposome susceptibility to the disruptive actions of melittin. Furthermore, melittin was demonstrated to induce liposome structural destabilization on a colloidal scale which coincided with leakage induction for both anionic and zwitterionic systems. The latter findings thus clearly show that coalescence, aggregation, and fragmentation contribute to melittin-induced liposome leakage, and that detailed molecular analyses of melittin pore formation are incomplete without considering also these colloidal aspects.
Strömstedt
Adam A
AA
Department of Pharmacy, Uppsala University, P.O. Box 580, SE-751 23 Uppsala, Sweden. adam.stromstedt@farmaci.uu.se
Wessman
Per
P
Ringstad
Lovisa
L
Edwards
Katarina
K
Malmsten
Martin
M
D008051:Lipid Bilayers / Q000737:chemistry*; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry; D008555:Melitten / Q000737:chemistry*; D010316:Particle Size; D013499:Surface Properties
D008051:Lipid Bilayers; D008055:Lipids; D008081:Liposomes; D008555:Melitten