Kinetics and Thermodynamics of the Association of Dehydroergosterol with Lipid Bilayer Membranes

We have examined the detailed kinetics and thermodynamics of the association of Ergosta-5,7,9(11),22-tetraen-3β-ol (dehydroergosterol, DHE) with lipid bilayers prepared from 1-palmitoyl-2-oleoylphosphatidylcholine (POPC), a 1:1 binary mixture of POPC and cholesterol (Chol), and a 6:4 binary mixture of egg sphingomyelin (SpM) and Chol. Association of DHE with all three membranes was shown to be entropically driven, most so in the case of SpM-Chol bilayers. Equilibrium partition coefficients for partitioning of DHE between the lipid phase and the aqueous phase were shown to be similar for POPC and POPC-Chol bilayers between 15 and 35°C. Partitioning into the SpM-Chol bilayer is favored at higher temperatures and there is a crossover in solubility preference at ∼25°C. Insertion (k+) and desorption (k−) rate constants were shown to be very similar for POPC and POPC-Chol bilayer membranes, but were lower for SpM-Chol bilayers. Similar results were previously reported by us for the association of other amphiphiles with these membranes. We propose a model for the microscopic structure of a POPC-Chol (1:1) bilayer membrane that is consistent with these observations.