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- Title
Miscibility and Stability of Sterol/Phospholipid Bilayers are Optimized by the Double Bond Position in the Sterol Nucleus.
- Authors
Benesch, Matthew G. K.; Mannock, David A.; Lewis, Ruthven N. A. H.; McElhaney, Ronald N.
- Abstract
Understanding the variation in the strength, number and types of interactions between the sterol ring system and neighboring phospholipid molecules is important in understanding the structure and function of sterol-containing membranes. This has important implications in treating sterol-involved pathological processes such as Parkinson's, Alzheimer's and prion-associated diseases, as well as some cancers. In this study, we investigated how the presence, position and conjugation of the carbon 5,6 double bond in ring B of cholesterol influences the thermotropic phase behavior of binary dipalmitoylphosphatidylcholine (DPPC, a model mammalian lipid)/sterol mixtures using differential scanning calorimetry and Fourier-transform infrared spectroscopy. Being fully miscible in a DPPC bilayer, cholesterol stabilizes the gel phase and reduces the enthalpy and cooperativity of the DPPC gel/liquid crystalline phase transition, eliminating its enthalpy by 50 mol% sterol. None of the other sterols studied have all these abilities. Generally, we see than an all-trans ring system is required to stabilize the gel phase, and the presence of a single double bond within ring A or B to abolish the phase transition at high sterol levels. All sterols in this study (equatorially-orientated carbon 3β-alcohols) broaden and the phase transition better than corresponding axially-orientated carbon 3α-alcohols and carbon 3-ketones. Further, a conjugated double-bond system may give rise to additional electronic properties that lead to an increased favorability in interactions between like-like (sterol) molecules over like-unlike (sterol-lipid) molecules, the latter being a necessary condition for optimal sterol/lipid miscibility and stability. Given the differences in the thermodynamic parameters obtained from DPPC mixtures containing different sterol ring conformations and their associated changes in bilayer stability and miscibility, it is clear that sterol conformation has a significant effect on bilayer physical properties. Any sterol molecule whose ring structure deviates from that of cholesterol is unlikely to be fully miscible in the mammalian cell membrane.
- Subjects
STEROLS; PHOSPHOLIPIDS; CELL nuclei; CALORIMETRY; THERMODYNAMICS
- Publication
UBC Medical Journal, 2011, Vol 2, Issue 2, p37
- ISSN
1920-7425
- Publication type
Abstract