Location of hexane in lipid bilayers determined by neutron diffraction

Abstract

Knowledge of the interactions of alkanes and other small hydrophobic molecules dissolved in lipid bilayers is important for understanding lipid–protein interactions in membranes1, the microscopic properties of solutions2,3 and the mechanism of anaesthesia4–6. An essential element for describing these interactions is the distribution of the molecules across the thickness of the bilayer. Studies of black lipid films1,2,7–9 strongly suggest that dissolved alkanes are located primarily in the centre of the bilayer. Recent X-ray and neutron diffraction and thermodynamic measurements on lipid dispersions and oriented lipid multilayers are consistent with this view10–12. We present here the first direct evidence for this hypothesis obtained from neutron diffraction studies of oriented dioleoyl lecithin (DOL) multilayers containing deuterated hexane introduced using the vapour phase. The hexane is found mainly in a zone 10 A wide in the centre of the bilayer. We have also estimated the amount of hexane in the bilayers and the free energy of transfer from pure hexane to bilayer. Our numbers are considerably different from those reported by Simon et al.13 for the interaction of hexane with DOL liposomes. The differences may be due to difference in water activity and bilayer curvature14.