The Effect of Cholesterol on the Lateral Diffusion of Phospholipids in Oriented Bilayers

Филиппов, А. В.; Orädd, Greger; Lindblom, Göran

doi:10.1016/s0006-3495(03)70033-2

Cited by 399 publications

(461 citation statements)

References 44 publications

(59 reference statements)

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“…Therefore, we estimate r m 1nm. Phospholipid bilayers in the fluid phase and in vitro typically have a diffusion coefficient D ≈ 1 − 10 × 10 −12 m 2 /s [23]. In our model, D ≈ 0.015 r 2 m /τ .…”

Section: Model and Methodsmentioning

confidence: 82%

Computer simulation of cytoskeleton-induced blebbing in lipid membranes

et al. 2011

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Blebs are balloon-shaped membrane protrusions that form during many physiological processes. Using computer simulation of a particle-based model for self-assembled lipid bilayers coupled to an elastic meshwork, we investigated the phase behavior and kinetics of blebbing. We found that blebs form for large values of the ratio between the areas of the bilayer and the cytoskeleton. We also found that blebbing can be induced when the cytoskeleton is subject to a localized ablation or a uniform compression. The results obtained are qualitatively in agreement with the experimental evidence and the model opens up the possibility to study the kinetics of bleb formation in detail.

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Section: Model and Methodsmentioning

confidence: 82%

Computer simulation of cytoskeleton-induced blebbing in lipid membranes

et al. 2011

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“…Lipid extracts form gel-phase membrane domains The difference in lipid diffusion constants between l o and l d (about a factor of three 28,29 ) is relatively small, and lipids appear to be able to pass through the boundaries between l d and l o phases. Therefore, formation of liquid ordered domains may slow down lipid diffusion but will not produce confinement of (Fig.…”

Section: Ordered Fraction Increases Below 40 1cmentioning

confidence: 99%

Progressive ordering with decreasing temperature of the phospholipids of influenza virus

Polozov¹,

Bezrukov²,

Gawrisch³

et al. 2008

Nat Chem Biol

200

159

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Using linewidth and spinning sideband intensities of lipid hydrocarbon chain resonances in proton magic angle spinning NMR spectra, we detected the temperature-dependent phase state of naturally occurring lipids of intact influenza virus without exogenous probes. Increasingly, below 41 1C ordered and disordered lipid domains coexisted for the viral envelope and extracts thereof. At 22 1C much lipid was in a gel phase, the fraction of which reversibly increased with cholesterol depletion. Diffusion measurements and fluorescence microscopy independently confirmed the existence of gel-phase domains. Thus the existence of ordered regions of lipids in biological membranes is now demonstrated. Above the physiological temperatures of influenza infection, the physical properties of viral envelope lipids, regardless of protein content, were indistinguishable from those of the disordered fraction. Viral fusion appears to be uncorrelated to ordered lipid content. Lipid ordering may contribute to viral stability at lower temperatures, which has recently been found to be critical for airborne transmission.Membranes of most enveloped viruses form by budding out from the plasma membranes of their host cells a highly select subset of plasma membrane components. In general, the selected membrane proteins are coded by the viral genome, whereas lipids are recruited from host membranes; however, the lipid composition of the viral envelope differs from that of the host membrane 1,2 and from other budding viruses 3 . The envelope of influenza contains higher amounts of both cholesterol 1 and glycosphingolipids 4 -lipids known to partition into the liquid ordered (l o ) phase. The l o phase is characterized by extended hydrocarbon chains having a reduced gauche-trans isomerization compared with those of the liquid disordered (l d ) phase, but having a similar rotational and translational mobility 5 . Liquid ordered phases are thought to be at the core of lipid rafts 6 , which are defined as transient membrane microdomains that are enriched in sphingolipids and cholesterol (1) 7 -a hypothesis that has generated much debate 8,9 .The influenza virus has played a pivotal role in the development of the raft hypothesis, starting with early studies that inferred ordered domains using spin probes 10-12 and fluorescence 13,14 and that suggested that an ordered lipid domain is selected in toto as the envelope during budding from the plasma membrane 15 . These lipids are either selected at the time of budding or pre-selected as the 'pre-envelope' suggested by clusters of the viral envelope protein hemagglutinin seen in immunoelectron microscopy 16 .Although detection of virus-sized domains of lipids (B100-nm diameter) is below the limit of resolution of fluorescent microscopy, large micrometer-sized membrane domains are reliably detected [17][18][19] . Recently, proton magic angle spinning NMR ( 1 H MAS NMR) has been used to determine the phase diagram of the same lipid compositions used to study large membrane domains in lipid bilayers and othe...

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“…[9][10][11] The available experimental methods can either directly determine the phase boundaries (DSC) or yield information on structural, mechanical, or dynamical changes (NMR, X-ray, fluorescence). Therefore, the comparison between the phase diagram and the different diagrams showing structural, mechanical, or dynamical changes is not straightforward.…”

Section: Introductionmentioning

confidence: 99%

Molecular Simulation of the DMPC-Cholesterol Phase Diagram

et al. 2010

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In this paper, we present a coarse-grained model of a hydrated saturated phospholipid bilayer (dimyristoylphosphatidylcholine, DMPC) containing cholesterol that we study using a hybrid dissipative particle dynamics-Monte Carlo method. This approach allows us to reach the time and length scales necessary to study structural and mechanical properties of the bilayer at various temperatures and cholesterol concentrations. The properties studied are the area per lipid, condensation, bilayer thickness, tail order parameters, bending modulus, and area compressibility. Our model quantitatively reproduces most of the experimental effects of cholesterol on these properties and reproduces the main features of the experimental phase and structure diagrams. We also present all-atom simulation results of the system and use these results to further validate the structure of our coarse-grained bilayer. On the basis of the changes in structural properties, we propose a temperature-composition structure diagram, which we compare with the experimental phase and structure diagrams. Attention is paid to the reliability and interpretation of the model and simulation method and of the different experimental techniques. The lateral organization of cholesterol in the bilayer is discussed.

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The Effect of Cholesterol on the Lateral Diffusion of Phospholipids in Oriented Bilayers

Cited by 399 publications

References 44 publications

Computer simulation of cytoskeleton-induced blebbing in lipid membranes

Computer simulation of cytoskeleton-induced blebbing in lipid membranes

Progressive ordering with decreasing temperature of the phospholipids of influenza virus

Molecular Simulation of the DMPC-Cholesterol Phase Diagram

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