Effect of small molecules on the dipalmitoyl lecithin liposomal bilayer: III. Phase transition in lipid bilayer

Summary The effect of more than ninety lipid-soluble compounds on the phase transition behavior ofdl--dipalmitoyl lecithin bilayer has been examined by differential scanning calorimetry. The type of effect on the phase transition profile depends on the nature of the additive, whereas the extent of the effect depends on the concentration. The compounds examined include uncouplers, alkanols, fatty acids, detergents, organic solvents, ionophores, inorganic ions, and some commonly used spin-labelled and fluorescent membrane probes. A qualitatively distinct effect of several of these additives on the phase transition behavior of bilayer provides a method of determining the nature of the perturbation they induce in the bilayer organization. The observations are consistent with the hypothesis that the type of effect induced by an additive on the phase transition profile of the bilayer is related to the position of localization of the additive along the thickness of the bilayer. At least four different types of modified transition profiles that are related to changes in bilayer fluidity can be distinguished. These correspond to the localization of the additive in phosphorylcholine (type D), glycerol backbone (type B), C₁–C₈ methylene (type A), C₉–C₁₆ methylene (type C) region of the bilayer. A possible relationship between the type of phase transition profiles of modified liposomes and the physiological effects of drugs is also discussed.