Effect of cholesterol and cholesterol derivatives on hydrocarbon chain mobility in lipids

Department of Chemistry, Sheffield University, Sheffield S3 7HF. England
Biochemical and Biophysical Research Communications (Impact Factor: 2.3). 06/1971; 43(3):610-6. DOI: 10.1016/0006-291X(71)90658-9
Source: PubMed


Cholesterol inhibits the chain motion of egg yolk lecithin when it is in the liquid crystalline phase. It also removes the sharp transition from gel to liquid crystalline phase normally observed with a saturated lipid such as dipalmitoyl lecithin. A similar lipid state is produced, partially characterised by a spin probe correlation time τc∼2 × 10−8s.Small modifications to the cholesterol structure cause marked alterations in the solubilisation properties of the resultant steroid in lecithin bilayer systems.

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    • "The powder pattern of DMPC:SM (1:1) is more rounded and typical of phospholipids in a mixed phase, with a narrower quadrupolar splitting of 34 kHz compared to ∼ 55 kHz for the cholesterol compositions. The more fluid acyl chains were more disordered in the absence of cholesterol compared to the liquid ordered phase of cholesterol-phospholipid bilayers [23], as seen in Fig. 2. An increase in temperature to 45 °C resulted in a small change in the 2 H spectra of the cholesterolcontaining MLV dispersions. "
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    ABSTRACT: Equinatoxin II (EqtII) is a pore-forming protein from Actinia equina that lyses red blood cell and model membranes. Lysis is dependent on the presence of sphingomyelin (SM) and is greatest for vesicles composed of equimolar SM and phosphatidylcholine (PC). Since SM and cholesterol (Chol) interact strongly, forming domains or "rafts" in PC membranes, (31)P and (2)H solid-state NMR were used to investigate changes in the lipid order and bilayer morphology of multilamellar vesicles comprised of different ratios of dimyristoylphosphatidylcholine (DMPC), SM and Chol following addition of EqtII. The toxin affects the phase transition temperature of the lipid acyl chains, causes formation of small vesicle type structures with increasing temperature, and changes the T(2) relaxation time of the phospholipid headgroup, with a tendency to order the liquid disordered phases and disorder the more ordered lipid phases. The solid-state NMR results indicate that Chol stabilizes the DMPC bilayer in the presence of EqtII but leads to greater disruption when SM is in the bilayer. This supports the proposal that EqtII is more lytic when both SM and Chol are present as a consequence of the formation of domain boundaries between liquid ordered and disordered phases in lipid bilayers leading to membrane disruption.
    Biochimica et Biophysica Acta 10/2009; 1798(2):244-51. DOI:10.1016/j.bbamem.2009.10.012 · 4.66 Impact Factor
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    • "The results of our DSC studies of binary mixtures of natural or enantiomeric cholesterol and egg SpM are also in excellent agreement with previous DSC studies of the thermotropic phase behavior of binary mixtures of natural cholesterol with various naturally occurring SpMs (Oldfield and Chapman, 1971; Calhoun and Shipley, 1979; Estep et al., 1979; McKeone et al., 1986; Chien et al., 1991; Chi et al., 1992; McIntosh et al., 1992b). In all of these studies, the incorporation of increasing quantities of cholesterol into SpM bilayers results in small shifts in the temperature and large decreases in the enthalpy and cooperativity of the gel/ liquid-crystalline phase transition, with this phase transition being completely abolished at 50 mol % cholesterol. "
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    ABSTRACT: Phospholipids, sphingolipids, and sterols are the major lipid components of the plasma membranes of eukaryotic cells. Because these three lipid classes occur naturally as enantiomerically pure compounds, enantiospecific lipid-lipid and lipid-sterol interactions could in principle occur in the lipid bilayers of eukaryotic plasma membranes. Although previous biophysical studies of phospholipid and phospholipid-sterol model membrane systems have consistently failed to observe such enantiomerically selective interactions, a recent monolayer study of the interactions of natural and enantiomeric cholesterol with egg sphingomyelin has apparently revealed the existence of enantiospecific sterol-sphingolipid interactions. To determine whether enantiospecific sterol-sphingolipid interactions also occur in more biologically relevant lipid-bilayer systems, differential scanning calorimetric, x-ray diffraction, and neutral buoyant-density measurements were utilized to study the effects of natural and enantiomeric cholesterol on the thermotropic phase behavior and structure of egg sphingomyelin bilayers. The calorimetry experiments show that the natural and enantiomeric cholesterol have essentially identical effects on the temperature, enthalpy, and cooperativity of the gel/liquid-crystalline phase transition of egg sphingomyelin bilayers within the limits of experimental error. As well, the x-ray diffraction and neutral buoyancy experiments indicate that bilayers formed from mixtures of natural or enantiomeric cholesterol and egg sphingomyelin have, within experimental uncertainty, the same structure and mass density. We thus conclude that significant enantioselective cholesterol-sphingolipid interactions do not occur in this lipid-bilayer model membrane system.
    Biophysical Journal 03/2003; 84(2 Pt 1):1038-46. DOI:10.1016/S0006-3495(03)74920-0 · 3.97 Impact Factor
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    • "It was suggested a half-century ago, based on x-ray diffraction and polarized light studies of myelin sheath of nerve, that cholesterol molecules complex with phospholipids and/or cerobrosides (Finean, 1953). By the early 1970s it had been shown that cholesterol and sphingomyelin (SPM) do, in fact, preferentially interact with each other in model membranes (Oldfield and Chapman, 1971, 1972; Long et al., 1971). This was followed by explorations of whether ordered domains of cholesterol and SPM exist in biological membranes (Goodsaid-Zalduondo et al., 1982), the demonstration that cholesterol must be present for capping of surface immunoglobulins on lymphocytes (Hoover et al., 1983), and the realization that some proteins might concentrate into microscopic domains rich in glycosphingolipids (Thompson and Tillack, 1985). "
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    ABSTRACT: Lipids segregate with each other into small domains in biological membranes, which can facilitate the associations of particular proteins. The segregation of cholesterol and sphingomyelin (SPM) into domains known as rafts is thought to be especially important. The formation of rafts was studied by using planar bilayer membranes that contained rhodamine-phosphatidylethanolamine (rho-DOPE) as a fluorescent probe, and wide-field fluorescence microscopy was used to detect phase separation of the probe. A fluorescently labeled GM(1), known to preferentially partition into rafts, verified that rho-DOPE faithfully reported the rafts. SPM-cholesterol domains did not form at high temperatures but spontaneously formed when temperature was lowered to below the melting temperature of the SPM. Saturated acyl chains on SPMs therefore promote the formation of rafts. The domains were circular (resolution > or = 0.5 microm), quickly reassumed their circular shape after they were deformed, and merged with each other to create larger domains, all phenomena consistent with liquid-ordered (l(o)) rather than solid-ordered (s(o)) domains. A saturated phosphatidylcholine (PC), disteoryl-PC, could substitute for SPM to complex with cholesterol into a l(o)-domain. But in the presence of cholesterol, a saturated phosphatidylethanolamine or phosphatidylserine yielded s(o)-domains of irregular shape. Lipids with saturated acyl chains can therefore pack well among each other and with cholesterol to form l(o)-domains, but domain formation is dependent on the polar headgroup of the lipid. An individual raft always extended through both monolayers. Degrading cholesterol in one monolayer with cholesterol oxidase first caused the boundary of the raft to become irregular; then the raft gradually disappeared. The fluid nature of rafts, demonstrated in this study, may be important for permitting dynamic interactions between proteins localized within rafts.
    Biophysical Journal 09/2001; 81(3):1486-500. DOI:10.1016/S0006-3495(01)75803-1 · 3.97 Impact Factor
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