1-2-oleoylphosphatidylcholine and 7-dehydrocholesterol

Despite extensive studies, the remarkable structure-function relationship of cholesterol in cellular membranes has remained rather elusive. This is exemplified by the fact that the membrane properties of cholesterol are distinctly different from those of many other sterols. Here we elucidate this issue through atomic-scale simulations of desmosterol and 7-dehydrocholesterol (7DHC), which are immediate precursors of cholesterol in its two distinct biosynthetic pathways. While desmosterol and 7DHC differ from cholesterol only by one additional double bond, we find that their influence on saturated lipid bilayers is substantially different from cholesterol. The capability to form ordered regions in a saturated (dipalmitoyl-phosphatidylcholine) membrane is given by cholesterol > 7DHC > desmosterol, indicating the important role of cholesterol in saturated lipid environments. For comparison, in an unsaturated (dioleoyl-phosphatidylcholine) bilayer, the membrane properties of all sterols were found to be essentially identical. Our studies indicate that the different membrane ordering properties of sterols can be characterized by a single experimentally accessible parameter, the sterol tilt. The smaller the tilt, the more ordered are the lipids around a given sterol. The molecular level mechanisms responsible for tilt modulation are found to be related to changes in local packing around the additional double bonds.

Topics: 1,2-Dipalmitoylphosphatidylcholine; Cell Membrane; Cholesterol; Dehydrocholesterols; Desmosterol; Lipid Bilayers; Models, Molecular; Molecular Conformation; Phosphatidylcholines; Water

The ESR spectra of cholestane spin labels (CSL) in dioleoylphosphatidylcholine (DOPC) bilayers containing 20 wt% of cholesterol, 7-dehydrocholesterol, beta-sitosterol, stigmasterol and lanosterol exhibit a marked similarity, thus indicating that these steroids induced the same effects on the lipid bilayer over the temperature range 21-55 degrees C. The incorporation of these steroids into the DOPC bilayers enhances the orientational order of the CSL molecules at every temperature studied, but only induces a pronounced slow-down in their rotational motions at temperatures above 35 degrees C. Similar results were obtained in DOPC/ergosterol multilamellar liposomes, but the changes are now less pronounced than in the other five DOPC/steroid systems. In contrast, the addition of stigmasterol to digalactosyldiacylglycerol (DGDG) bilayers appears to increase the order parameter mean value of P2, without affecting the diffusion coefficients. Furthermore, the incorporation of 7-dehydrocholesterol to DGDG bilayers causes a large enhancement in the orientational order, but has only a small effect on D perpendicular of the CSL molecules. Importantly, this latter effect appears to be independent of temperature. The marked changes in the rates of the rotational motion brought about by the addition of steroids, contrasts with the lack of a significant effect of unsaturation on the bilayer dynamics reported by us previously (Korstanje et al. (1989), Biochim. Biophys. Acta 980, 225-233, and 982, 196-204).

Topics: Chemical Phenomena; Chemistry, Physical; Cholestanes; Cholesterol; Dehydrocholesterols; Electron Spin Resonance Spectroscopy; Galactolipids; Glycolipids; Lanosterol; Lipid Bilayers; Liposomes; Phosphatidylcholines; Sitosterols; Spin Labels; Steroids; Stigmasterol; Structure-Activity Relationship; Temperature