Multi-Nuclear NMR Studies of Phospholipid Membranes and their Interaction with Membrane Active Substances

  • Jeffrey Veiro

    Student thesis: Doctoral Thesis


    Multinuclear magnetic resonance spectroscopy in conjunction with lanthanide shift reagents was used to investigate the interaction of unilamellar phospholipid vesicles with membrane active substances.

    The regulation of ion channels by lipids such as the phosphatidic acids was investigated using 1H-NMR and small phospholipid vesicles. Transport across lipid vesicles in the presence of the ionophores alamethicin, melittin and nystatin was monitored using the lanthanide probe ion Pr3+. Channel characteristics were found to be dependent upon molecular interactions between the lipid and the individual ionophores. The results were discussed in terms of the phosphatidylinositol effect.

    The NMR technique provided methods whereby intervesicle ionophore exchange was studied. The results revealed that ionophore exchange between vesicles, the mechanism of exchange and the rate of ion conduction were dependent upon the initial environment of the ionophore and also the lipid composition of the vesicle.

    The modulation of a variety of mechanisms of channel-mediated transport across small phospholipid vesicles by a range of general anaesthetics were investigated using 1H-NMR. Membrane permeability was found to be inhibited by inhalation anaesthetics independently of the channel system or lipid composition used. The results indicated the importance of hydrogen bonding as an explanation of the observed inhibition. 19F-NMR was used to monitor signals from the fluorinated anaesthetics themselves, the results providing information on the disposition of the anaesthetics within the bilayer.

    23Na + and 7Li transport across large vesicles was monitored using 23Na+ and 7Li+-NMR. The effect of the general anaesthetics on ion transport was found to be dependent upon the ionophore and the type of metal ions present in the vesicular solution, further suggesting the importance of hydrophilic interactions of the anaesthetics.

    Finally, 31P-NMR was used to show the inhibition by general anaesthetics of the hydrolysis of glucose-6-phosphate by the enzyme glucose-6-phosphatase which further supported the above conclusions on anaesthetic action.
    Date of AwardNov 1985
    Original languageEnglish
    Awarding Institution
    • Polytechnic of Wales

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