Changes of conductance and compressibility of bilayer lipid membranes induced by oligonucleotide-cationic polyene antibiotic complexes.
The positively charged polyene molecule amphotericin B 3-dimethylaminopropylamide (AMA) is an efficient agent for the delivery of antisense oligodeoxyribonucleotides (ODN) into target cells. In the present study, bilayer lipid membrane (BLM) conductance, elasticity modulus perpendicular to the membrane plane, surface potential and electrical capacitance were measured by conductance and electrostriction methods in the presence of AMA, pure or complexed to 20-mer single stranded ODN at different ratios. Pure AMA did not induce changes in conductance of cholesterol-containing BLM, but did induce an increase in elasticity modulus and surface potential. ODN/AMA complexes changed BLM properties depending on the charge ratio. The most pronounced effect on membrane conductance was observed for positively charged ODN/AMA complexes (charge ratio rho-/+=0.1), while for negatively charged complexes these changes were less marked/apparent, correlating to substantially lower binding constants. The effect of ODN/AMA complexes on elasticity modulus and charge potential was biphasic. After an increase in both values, a decrease was observed for higher incubation times and ODN/AMA concentrations. These results are interpreted as indicating that the membrane property changes result from the large AMA aggregates induced by the presence of the negatively charged ODN, which condensate on these aggregates. It is suggested that the decrease of elasticity modulus and surface potential in the presence of increasing incubation time and AMA concentration result from desorption of the complexes in the complex-free compartment of the BLM cell, or appearance of a non-linear conductance of the lipid bilayer. The first alternative would explain the AMA-induced transmembrane transfer of ODN.
Hianik
Tibor
T
Department of Nuclear Physics and Biophysics, Faculty of Mathematics, Physics and Computer Science, Comenius University, Mlynská dolina F1, 842 48 Bratislava, Slovak Republic. hianik@fmph.uniba.sk
Ostatnik
Lukas
L
Polohova
Vladimira
V
Bolard
Jacques
J
D000666:Amphotericin B / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry* / Q000494:pharmacology; D004548:Elasticity; D004553:Electric Conductivity; D008051:Lipid Bilayers / Q000378:metabolism*; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage / Q000494:pharmacology*; D011090:Polyenes / Q000494:pharmacology
D023181:Antimicrobial Cationic Peptides; D004337:Drug Carriers; D008051:Lipid Bilayers; D009838:Oligodeoxyribonucleotides; D016376:Oligonucleotides, Antisense; D011090:Polyenes; C408366:amphotericin B3-(N'-dimethylamino)propylamide; D000666:Amphotericin B