title: Interaction of gentamicin polycation with model and cell membranes.
abstract: The interaction of positively-charged antibiotic gentamicin with cell membranes was studied to determine if any changes in membrane organization were induced by the drug. Opossum kidney epithelia (OK) cells were used as models of eukaryotic cells. Two methods were used: laurdan fluorescence spectroscopy and fluorescence anisotropy recordings on 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene p-toluenesulfonate (TMA-DPH) labeled cell suspensions. Both methods showed an altered membrane hydration and fluidity of gentamicin treated cells. Liposomes prepared from dimyristoyl-phosphatidylcholine (DMPC) mixed with cardiolipin, which mimics the heterogeneous charge composition of the natural cell membrane, were used to determine the effect of gentamicin on artificial bilayers. The membrane lipid packing as revealed by generalized polarization (GP) and fluorescence anizotropy variation with increasing temperature was studied. It was found that the generalized polarization of liposomal membranes containing a negatively charged lipid (cardiolipin) is higher in the presence of gentamicin; in the membrane of living cell (OK), gentamicin induces, on the contrary, a decrease of general polarization. Considering the role of membrane organization in the function of transmembrane channels and receptors, our findings suggest hypotheses that may explain the permeation of gentamicin through the living cell membrane by using these channels.
authors.affiliation: Carol Davila Medical and Pharmaceutical University, Biophysics and Cellular Biotechnology Department, Bucharest, Romania.
authors.forename: Eugenia
authors.initials: E
authors.lastname: Kovács
authors.forename: Tudor
authors.initials: T
authors.lastname: Savopol
authors.forename: Maria-Minodora
authors.initials: MM
authors.lastname: Iordache
authors.forename: Lavinia
authors.initials: L
authors.lastname: Săplăcan
authors.forename: Iuliana
authors.initials: I
authors.lastname: Sobaru
authors.forename: Claudia
authors.initials: C
authors.lastname: Istrate
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Mingeot-Leclercq
authors.forename: Mihaela-Georgeta
authors.initials: MG
authors.lastname: Moisescu
mesh_terms: D015081:2-Naphthylamine / Q000031:analogs & derivatives; D000818:Animals; D001692:Biological Transport; D002308:Cardiolipins / Q000737:chemistry; D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry; D004161:Diphenylhexatriene / Q000031:analogs & derivatives; D004847:Epithelial Cells / Q000737:chemistry* / Q000166:cytology / Q000378:metabolism; D005454:Fluorescence Polarization; D005456:Fluorescent Dyes; D005839:Gentamicins / Q000737:chemistry*; D007668:Kidney / Q000737:chemistry* / Q000166:cytology / Q000378:metabolism; D007848:Laurates; D008081:Liposomes / Q000737:chemistry*; D008563:Membrane Lipids / Q000737:chemistry*; D008567:Membranes, Artificial; D009893:Opossums; D011073:Polyamines / Q000737:chemistry; D000071228:Polyelectrolytes; D013050:Spectrometry, Fluorescence; D055672:Static Electricity
chemical_list: D015081:2-Naphthylamine; D002308:Cardiolipins; D004134:Dimyristoylphosphatidylcholine; D004161:Diphenylhexatriene; D005456:Fluorescent Dyes; D005839:Gentamicins; D007848:Laurates; D008081:Liposomes; D008563:Membrane Lipids; D008567:Membranes, Artificial; D011073:Polyamines; D000071228:Polyelectrolytes; C033628:1-(4-(trimethylamino)phenyl)-6-phenylhexa-1,3,5-triene; C065580:laurdan