Amine spin probe permeability in sonicated liposomes.

Permeabilities for an homologous series of amine nitroxide spin probes were measured in liposomes of varying composition by an electron paramagnetic resonance (EPR) method. Results show that the rate-limiting step in permeation is not adsorption/desorption at the aqueous/membrane interface for two probes in phosphatidylcholine/phosphatidic acid liposomes and for one probe in phosphatidylcholine/cholesterol/phosphatidic acid liposomes. Accordingly, we interpret observed selectivity patterns for the entire series of probes in liposomes and red cells in terms of the properties of the bilayer interior. Results are inconsistent with simple applications of either free volume or hydrocarbon sheet models of nonelectrolyte permeation. In the former case, it was found that liposomes do not select against these probes on the basis of molecular volume. In the latter case, probe permeabilities are all much lower than would be predicted for a sheet of bulk hydrocarbon and the polarity of the rate-limiting region is shown to be greater than bulk hydrocarbon. Together with the results of previous studies of spin-labeled solutes in membranes, as well as studies of lipid dynamics in membranes, these latter results suggest that the rate-limiting region in nonelectrolyte permeation is not in the center of the bilayer, but in the relatively ordered acyl chain segments near the glycerol backbone.