The RH 421 styryl dye induced, pore model-dependent modulation of antimicrobial peptides activity in reconstituted planar membranes.
BACKGROUND
Antimicrobial agents, with different pore-formation mechanisms, may be differently influenced by alteration of the dipolar electric field of a lipid membrane.


METHODS
By using electrophysiological measurements on reconstituted lipid membranes, we used alamethicin, melittin and magainin to report on how controlled manipulation of the membrane dipole potential by the styrylpyridinium dye RH 421 affects the kinetic and transport features of peptides within membranes.


RESULTS
Our data demonstrate that the increase of the membrane dipole potential caused by RH 421 decreases the activity and single-channel conductance of alamethicin. Surprisingly, we found that RH 421 increases the activity of melittin and magainin, suggesting that RH 421 may contribute via electrostatic repulsions, among others, to an increase in the monolayer spontaneous curvature of the membrane. We propose that RH 421-induced dipole potential and membrane elasticity changes alter the peptide-induced channel dynamics, and the prevalence of one mechanism over the other for particular classes of peptides is dictated by the electrical and mechanical interactions which rule the pore-formation mechanism of such peptides.


CONCLUSIONS
These results point to a novel paradigm in which electrical and mechanical effects promoted by chemicals which preferentially alter the electrostatics of the membrane, may be employed to help distinguish among various pore-formation mechanisms of membrane-permeabilizing peptides.
Apetrei
Aurelia
A
'Al. I. Cuza' University, Faculty of Physics, Laboratory of Biophysics and Medical Physics, Blvd. King Carol I, No. 11, Iasi, R-700506, Romania.
Mereuta
Loredana
L
Luchian
Tudor
T
D000408:Alamethicin / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D004396:Coloring Agents / Q000494:pharmacology*; D004553:Electric Conductivity; D017136:Ion Transport / Q000187:drug effects; D008555:Melitten / Q000494:pharmacology; D008567:Membranes, Artificial; D008954:Models, Biological; D016062:Porosity / Q000187:drug effects; D011726:Pyridinium Compounds / Q000494:pharmacology*; D013343:Styrenes / Q000494:pharmacology*
D023181:Antimicrobial Cationic Peptides; D004396:Coloring Agents; D008567:Membranes, Artificial; D011726:Pyridinium Compounds; D013343:Styrenes; C070534:RH 421; D008555:Melitten; D000408:Alamethicin