Steroid structural requirements for stabilizing or disrupting lipid domains.

In artificial membrane bilayers, saturated long acyl chain-containing phospholipids and cholesterol (Chol) interact to form more ordered domains than those in phospholipids with unsaturated or short fatty acyl chains. We have extended the fluorescence techniques of London et al. [Xu, X., and London, E. (2000) Biochemistry 39, 843−849; Xu, X., Bittman, R., Duportail, G., Heissler, D., Vilchezes, C., and London, E. (2001) J. Biol. Chem. 276, 33540−33546] to study the propensity of several steroids to form or disrupt such ordered lipid domains. Temperature-dependent fluorescence quenching and steady-state polarization of the extrinsic fluorescent probe diphenylhexatriene (DPH) in model membranes composed of dipalmitoylphosphatidylcholine (or sphingomyelin), a nitroxide spin-labeled phosphatidylcholine (12-SLPC), and a given steroid were combined to study the influence of the latter on (a) ordered lipid domain formation, (b) stabilization, and (c) the extension of the ordered lipid assemblies. The results of ...