Lateral organization of cholesterol molecules in lipid-cholesterol assemblies

Sengupta, Pinaki; Singh, Rajiv R. P.; Cox, D. L.; Slepoy, Alexander

doi:10.1103/physreve.70.021902

Cited by 6 publications

(5 citation statements)

References 32 publications

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“…Several theoretical and experimental studies have suggested that sterols (e.g., cholesterol and ergosterol) tend to adopt regular, superlatticelike distributions in lipid bilayers, and PC bilayers in particular. ,, It has been proposed that cholesterol imposes steric strain in the acyl chain matrix, which drives cholesterol molecules toward a regular distribution . The same study provided evidence that some of the putative superlattices have a centered rectangular, rather than hexagonal, symmetry.…”

Section: Resultsmentioning

confidence: 99%

Solvent-Free Lipid Bilayer Model Using Multiscale Coarse-Graining

Izvekov

Voth

2009

J. Phys. Chem. B

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The multiscale coarse-graining (MS-CG) approach developed in our previous work is extended here to model solvent-free lipid bilayers. The water (solvent) molecules are completely integrated out of the coarse-grained (CG) effective force field. The MS-CG force field, a sum of pairwise central forces, accurately approximates the many-body potential of mean force in the coarse-grained coordinates. It thus incorporates both energetic and entropic contributions. To improve the stability and elastic properties of the MS-CG simulated bilayer, an additional constraint was adopted: the partial virial associated with CG bilayer sites was matched to its corresponding atomistic value for each configuration of the system. The resulting solvent-free MS-CG model reproduces a liquid-state lipid bilayer with accurate structural and elastic properties. Finally, the solvent-free MS-CG model is used to simulate a very large, flat bilayer and two liposome geometries, demonstrating its greatly enhanced computational efficiency.

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Section: Resultsmentioning

confidence: 99%

Solvent-Free Lipid Bilayer Model Using Multiscale Coarse-Graining

Izvekov

Voth

2009

J. Phys. Chem. B

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“…It was reported earlier that the miscibility of cholesterol increases significantly in the saturated phosphatidylcholine (PC) lipids in comparison to that in the unsaturated one. Previous reports concerning the PC–cholesterol interaction both in the Langmuir monolayer − and in the model bilayer ,,− have witnessed the cholesterol-induced structural changes in the phospholipid model membranes. Despite vivid research with model biomembranes, the phospholipid phase dependency of lateral and out-of-plane organization of cholesterols as a function of concentration is still not achieved satisfactorily and needs significant effort to understand the interaction mechanism.…”

Section: Introductionmentioning

confidence: 96%

Cholesterol-Induced Structural Changes in Saturated Phospholipid Model Membranes Revealed through X-ray Scattering Technique

2017

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Lateral and out-of-plane organization of cholesterol and its effect on regulating the physicochemical properties of zwitterionic phospholipid model membranes have been investigated by a pressure-area isotherm study from the Langmuir monolayer, atomic force microscopy (AFM), and X-ray reflectivity (XRR) measurements from supported binary monolayer films. The systematic isotherm studies on the Langmuir monolayer of phospholipids and the subsequent extraction of excess Gibbs free energy (ΔG) revealed the mechanism of cholesterol interaction and the molecular cooperativeness for different arrangements in the phospholipid model membranes. We have found a critical cholesterol molar concentration (χ) up to which the lipid-cholesterol miscibility gradually increases and then further increase in the concentration leads to an inhomogeneous structure formation similar to raft structures. The thickening in the lipid acyl chain and the subsequent lowering of the lipid head group thickness up to χ are also evident from the XRR study. Beyond χ, large-sized domains are observed in the AFM images from the deposited monolayer. χ has also been observed to depend on the phase of the monolayer, in particular, ∼25 molar % in the gel phase and ∼40 molar % in the fluid phase, wherein a regular distribution has been found with the highest separation between the cholesterol molecules. The extracted isothermal compressibility coefficient (C) and ΔG from the monolayer isotherms indicate that the molecular arrangement at χ are the most stable configurations of the monolayer. Our study provides direct evidence into cholesterol-induced evolution in phase behavior and the consequent model on the structure at different phases in the phospholipid Langmuir monolayers.

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“…x k G , y k G and φ k G in (16)- (18) are Gaussian random variables with zero mean and unit variance.…”

Section: Appendix: Discretization Of Stochastic Equationsmentioning

confidence: 99%

Self-consistent mean-field model based on molecular dynamics: Application to lipid-cholesterol bilayers

Khelashvili

Pandit

Scott

2005

The Journal of Chemical Physics

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We have developed a dynamic self-consistent mean-field model, based on molecular-dynamics simulations, to study lipid-cholesterol bilayers. In this model the lipid bilayer is represented as a two-dimensional lattice field in the lipid chain order parameters, while cholesterol molecules are represented by hard rods. The motion of rods in the system is continuous and is not confined to lattice cells. The statistical mechanics of chain ordering is described by a mean field derived from an extension of a model due to Marcelja. The time evolution of the system is governed by stochastic equations. The ensemble of chain configurations required in partition sums, and the energies of interaction, are taken from atomistic level molecular-dynamics simulations of lipid bilayers. The model allows us to simulate systems 500 nm in lateral size for 20 micros time scales, or greater. We have applied the model to dipalmitoyl-phosphatidylcholine-cholesterol (Chol) bilayers at 50 degrees C for Chol concentrations between 2% and 33%. At low concentrations of Chol (2%-4%), the model predicts the formation of isolated clusters of Chol surrounded by relatively ordered lipid chains, randomly dispersed in the disordered bilayer. With increasing Chol composition, regions of Chol-induced order begin to overlap. Starting from about 11% Chol this ordering effect becomes system wide and regions unaffected by Chol are no longer detectable. From the analysis of properties of the model we conclude that the change in lipid chain order with increasing Chol concentration is continuous over the 20-mus scale of the simulations. We also conclude that at 50 degrees C no large-scale Chol-rich and Chol-depleted coexisting phase-separated regions form at any concentration. At no point in any of the simulations do we observe a higher degree of lateral organization, such as Chol-based superlattice structures.

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Lateral organization of cholesterol molecules in lipid-cholesterol assemblies

Cited by 6 publications

References 32 publications

Solvent-Free Lipid Bilayer Model Using Multiscale Coarse-Graining

Solvent-Free Lipid Bilayer Model Using Multiscale Coarse-Graining

Cholesterol-Induced Structural Changes in Saturated Phospholipid Model Membranes Revealed through X-ray Scattering Technique

Self-consistent mean-field model based on molecular dynamics: Application to lipid-cholesterol bilayers

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