Lyotropic lipid phases confined in cylindrical pores: structure and permeability

A model membrane system based on lipid lyotropic phases confined inside the pores of a well-defined scaffold membrane, thereby forming a double-porous membrane structure, is described. The model membrane system is characterized with regard to lipid structure, lipid location, and phase transitions, using small-angle X-ray scattering, differential scanning calorimetry, and confocal microscopy. The system enables studies of transport across oriented lipid bilayers as well as of lipids in confinement. The lipids are shown to be located inside the membrane pores, and the effect of confinement on lipid structure is shown to be small, although dependent on the surface properties of the scaffold membrane. For transport studies, Franz diffusion cells and different types of drugs/dyes are used, and the transport studies are complemented with theoretical modeling. Lipids investigated include monoolein, dioleoyl phosphatidylcholine, dimyristoyl phosphatidylcholine, and E. coli total lipid extract. In the case of monoolein, the lipid structure can be changed from a bicontinuous cubic Ia3d phase to a liquid crystalline lamellar phase, by controlling the osmotic pressure of the surrounding solution through addition of water-soluble polymer. The osmotic pressure can thereby be used as a switch, changing the permeability of the lipid phase up to 100-fold, depending on the properties of the diffusing substance. The large effect of changing the structure implies an alignment of the lamellar phase inside the pores.