A Statistical Mechanical Model of Cholesterol/Phospholipid Mixtures: Linking Condensed Complexes, Superlattices, and the Phase Diagram

Sugár, István P.; Chong, Parkson L.-G.

doi:10.1021/ja2092322

Cited by 21 publications

(23 citation statements)

References 40 publications

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“…An alternate view that proposes a longer range, lattice-like substructure in the L o phase of binary mixtures containing cholesterol has been proposed by Chong and coworkers, with the lattice composed of condensed complexes of lipid and cholesterol. 52 …”

Section: Discussionmentioning

confidence: 99%

The Molecular Structure of the Liquid-Ordered Phase of Lipid Bilayers

et al. 2014

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Molecular dynamics simulations reveal substructures within the liquid-ordered phase of lipid bilayers. These substructures, identified in a 10 μsec all-atom trajectory of liquid-ordered/liquid-disordered coexistence (Lo/Ld), are composed of saturated hydrocarbon chains packed with local hexagonal order, and separated by interstitial regions enriched in cholesterol and unsaturated chains. Lipid hydrocarbon chain order parameters calculated from the Lo phase are in excellent agreement with 2H NMR measurements; the local hexagonal packing is also consistent with 1H-MAS NMR spectra of the Lo phase, NMR diffusion experiments, and small angle X-ray- and neutron scattering. The balance of cholesterol-rich to local hexagonal order is proposed to control the partitioning of membrane components into the Lo regions. The latter have been frequently associated with formation of so-called rafts, platforms in the plasma membranes of cells that facilitate interaction between components of signaling pathways.

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Section: Discussionmentioning

confidence: 99%

The Molecular Structure of the Liquid-Ordered Phase of Lipid Bilayers

et al. 2014

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“…Nevertheless, a number of investigators have found the evidence for the existence of relatively large, long-lived lipid rafts in actual biological membranes unconvincing (Edidin, 2003;McMullen et al, 2004;Munro, 2003). Moreover, other workers have provided evidence that Chol may be organized as molecular complexes (Radhakrishnan and McConnell, 1999) or various superlattices (Chong, 1994;Helrich et al, 2006;Huang, 2002;Sugar and Chong, 2012) in phospholipid bilayers, resulting in biphasic or discontinuous changes in some of their physical properties. Whatever the biophysical details, it is clear that the presence of Chol in biological membranes does modulate a number of different membrane functions, either directly or via its effects on the properties and lateral organization of the phospholipid bilayer (Dahl and Dahl, 1988,b;McElhaney, 1992a, b;Yeagle, 1988).…”

Section: Introductionmentioning

confidence: 99%

A DSC and FTIR spectroscopic study of the effects of the epimeric cholestan-3-ols and cholestan-3-one on the thermotropic phase behavior and organization of dipalmitoylphosphatidylcholine bilayer membranes: Comparison with their 5-cholesten analogs

Benesch

Lewis

Mannock

et al. 2015

Chemistry and Physics of Lipids

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We present the results of a comparative differential calorimetric and Fourier transform infrared spectroscopic study of the effect of cholesterol and five analogs on the thermotropic phase behavior and organization of dipalmitoylphosphatidylcholine bilayer membranes. These sterols/steroids differ in both the nature and stereochemistry of the polar head group at C3 (β-OH, α-OH or C=O) and in the presence or absence of a double bond in ring B. In both the Δ(5) and saturated sterols/steroid series, the concentration of these compounds required to abolish the DPPC pretransition, inversely related to their relative ability to disorder gel state DPPC bilayers, decreases in the order β-OH > α-OH > C=O. However, in the saturated series, these concentrations are much more similar, regardless of polar head group chemical structure. Similarly, the residual enthalpy of the DPPC main phase transition at 50 mol% sterol/steroid, inversely related to the miscibility of these compounds in fluid DPPC bilayers, also increases in the order β-OH > α-OH > C=O, but this effect is again attenuated in the saturated series. Moreover, replacement of the double bond at C5 with a saturated linkage also reduces sterol/steroid solubility in all cases. Interestingly, the C5 double bond has no effect on DPPC hydrocarbon chain ordering in the βOH sterol pair, considerably increases ordering in the αOH pair, and considerably reduces ordering in the C=O pair. Moreover, the ability of these compounds to order the DPPC hydrocarbon chains decreases in the order β-OH > α-OH > C=O in the Δ(5) series of compounds, but in the order β-OH > C=O > α-OH in the saturated series. Our results indicate that the effects of the presence or absence of a double bond at C5 of ring B on the thermotropic phase behavior and organization of DPPC bilayers are influenced by the nature and stereochemistry of the polar group present at C3 and vice versa. Nevertheless, the characteristic effects of sterols/steroids on fluid lipid bilayers are optimal when an OH group rather than C=O group is present at C3, and when this OH group is in the equatorial (β) orientation. Moreover, the presence of a single double bond specifically at C5 is required to maximize sterol solubility in fluid DPPC bilayers, which is probably its primary function in natural sterols.

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“…A statistical mechanical model of CHOL-phos pholipid mixtures that is able to rationalize almost any critical mole fraction value previously reported for ste rol superlattice formation as well as the observed biphasic changes in membrane properties was recently presented in paper [263]. According to this model, the extent and the type of sterol superlattices, and thus the lateral distribution of the entire membrane, should vary with CHOL mole fraction in a delicate, predict able, and nonmonotonic manner, which should have profound functional implications.…”

Section: Cholesterolmentioning

confidence: 89%

Computer simulation of lipid membranes: Methodology and achievements

Rabinovich

Lyubartsev

2013

Polym. Sci. Ser. C

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Rapid development of computer power during the last decade has made molecular simulations of lipid bilayers feasible for many research groups, which, together with the growing general interest in investi gations of these very important biological systems has lead to tremendous increase of the number of research on the computational modeling of lipid bilayers. In this review, we give account of the recent progress in com puter simulations of lipid bilayers covering mainly the period of the last 7 years, and covering only several selected subjects: methodological (development of the force fields for lipid bilayer simulations, use of coarse grained models) and scientific (studies of the role of lipid unsaturation, and the effect of cholesterol and other inclusions on properties of the bilayer).

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A Statistical Mechanical Model of Cholesterol/Phospholipid Mixtures: Linking Condensed Complexes, Superlattices, and the Phase Diagram

Cited by 21 publications

References 40 publications

The Molecular Structure of the Liquid-Ordered Phase of Lipid Bilayers

The Molecular Structure of the Liquid-Ordered Phase of Lipid Bilayers

A DSC and FTIR spectroscopic study of the effects of the epimeric cholestan-3-ols and cholestan-3-one on the thermotropic phase behavior and organization of dipalmitoylphosphatidylcholine bilayer membranes: Comparison with their 5-cholesten analogs

Computer simulation of lipid membranes: Methodology and achievements

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