Liposomes are synthetic vesicles comprised of bimolecular layers (bilayers) of phospholipids. They have been used as models of cell membranes (1), as drug delivery systems in which the drug is encapsulated within the liposome, and as carriers for genetic material into cells (see Transfection) (2). They are generally classified according to their size and the number of bilayers in the vesicle. Unilamellar vesicles consist of a single bilayer enclosing an aqueous core and may be small (SUVs) with a diameter of up to 300 A, or large (LUVs) with diameters comparable to cell membranes. Multilamellar vesicles may be 1 to 50 |im in diameter; in cross section, when viewed by electron microscopy, the structure appears onion-like in which the bilayers are concentrically arranged and separated by alternating aqueous layers. SUVs generally require special procedures for their preparation, such as sonication (3); multilamellar vesicles generally form spontaneously when phospholipids are dispersed in water. LUVs have structures most closely resembling the membrane; they may be prepared, but only with special techniques such as extrusion of multilamellar vesicles under pressure through small pore membranes (4). LUVs will form spontaneously in phospholipid dispersions and in surface films, but only at a critical temperature that depends on the phospholipid composition (5). If the total lipid composition of a cell membrane is used to form the aqueous dispersion, the critical temperature for spontaneous formation of LUVs is the physiological temperature of the cell from which the lipids are removed (6) (see Membranes).
Liposomes have also been utilized to examine the nature of the fundamental forces that exist between the phospholipid bilayers of multilamellar vesicles. An approach that has been especially informative is the osmotic stress method, in which the aqueous spacing between the bilayers is modified by osmotic pressure. This method utilizes bilayer-impermeable, water-soluble polymers in the suspending solution to create an osmotic gradient between the internal aqueous phase of liposomes and the external solution. Equilibration results in water being driven from the liposome until the interbilayer forces balance the osmotic pressure. From measurements of the equilibrium interbilayer spacing, using X-ray diffraction methods and its dependence on osmotic pressure, Rand and Parsegian (7) have obtained the contributions of hydration, electrostatic interactions, and van der Waals interactions to the internal energy of the multilamellar vesicles.
