Sphingomyelin-Cholesterol Domains in Phospholipid Membranes: Atomistic Simulation

Pandit, Sagar A.; Vasudevan, Sheeja V.; Chiu, See‐Wing; Mashl, R. Jay; Jakobsson, Eric; Scott, H. L.

doi:10.1529/biophysj.104.041939

Cited by 168 publications

(196 citation statements)

References 63 publications

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“…The most populated area per POPA is similar to that for POPC, presumably because of the structure similarity in their hydrocarbon chains. The area per CHOL for the system equilibrated for 50 ns is 30 Å 2 , which is close to the previously reported values of area per CHOL in the DOPC/SM/CHOL ternary mixture using the same Voronoi method 33,36 .…”

Section: Average Area Per Moleculesupporting

confidence: 88%

“…5 with experimental data due to their unavailability, but the most populated area per POPC in the histogram for the system of 50-ns simulations seems smaller than experimental value of 68.3±1.5 Å 2 obtained for a pure POPC preparation 40 . Smaller area per POPC molecule was also found in previous MD simulations for pure POPC and POPC mixture with CHOL 33,41 . The most populated area per POPA is similar to that for POPC, presumably because of the structure similarity in their hydrocarbon chains.…”

Section: Average Area Per Moleculesupporting

confidence: 81%

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Molecular Dynamics Simulations of Ternary Membrane Mixture: Phosphatidylcholine, Phosphatidic Acid, and Cholesterol

et al. 2007

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A ternary mixture of 1-palmitoyl-2-oleoyl phosphatidylcholine (POPC), 1-palmitoyl-2-oleoyl phosphatidic acid (POPA), and cholesterol (CHOL) works effectively for a functional conformation of nicotinic acetylcholine receptor (nAChR) that can undergo agonist-induced conformation changes, but POPC alone can stabilize only a desensitized state of nAChR. To gain insights into the lipid mixture that have strong impact to nAChR functions, we performed more than 50-ns all atom molecular dynamic (MD) simulations at 303 K on a fully hydrated bilayer consisting of 240 POPC, 80 POPA, and 80 CHOL (3:1:1). The MD simulation revealed various interactions between different types of molecular pairs that ultimately regulated lipid organization. The heterogeneous interactions among three different constituents resulted in a broad spectrum of lipid properties, including extensive distribution of average area per lipids and varied lipid ordering as a function of lipid closeness to CHOL. Higher percentage of POPA than POPC had close association with CHOL, which coincided with relatively higher ordering of POPA molecules in their acyl chains near lipid head groups. Lower fraction of gauche dihedrals was also found in the same region of POPA. Although the CHOL molecules had the effects on the enhancement of surrounding lipid order, relatively low lipid order parameters and high fraction of gauche bonds were observed in the ternary mixture. Collectively, these results suggest that the dynamical structure of the ternary system could be determinant for a functional nAChR.

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Section: Average Area Per Moleculesupporting

confidence: 88%

Section: Average Area Per Moleculesupporting

confidence: 81%

Molecular Dynamics Simulations of Ternary Membrane Mixture: Phosphatidylcholine, Phosphatidic Acid, and Cholesterol

et al. 2007

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“…In performing this umbrella function, the side chains of the phospholipids need to become more ordered to allow closer packing and crowding of the lipid head groups. A third and particularly interesting possibility is shown by computational modelling of the molecular interactions in a ternary mixture of cholesterol, 1,2-dioleoylphosphatidylcholine (DOPC) and sphingomyelin [53][54] . As the simulations evolve, cholesterol preferentially localizes at the interface between sphingomyelin-enriched and DOPC-enriched regions, with the saturated sphingomyelin acyl chains packing against the smooth α-face of cholesterol, and the disordered acyl chains of DOPC packing more easily against the opposite β-face, which is rougher because of protruding methyl groups 53 .…”

Section: Box 1 How Does Cholesterol Drive Domain Formation In Membranes?mentioning

confidence: 99%

Lipid rafts: contentious only from simplistic standpoints

Hancock

2006

Nat Rev Mol Cell Biol

751

716

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The hypothesis that lipid rafts exist in plasma membranes and have crucial biological functions remains controversial. The lateral heterogeneity of proteins in the plasma membrane is undisputed, but the contribution of cholesterol-dependent lipid assemblies to this complex, non-random organization promotes vigorous debate. In the light of recent studies with model membranes, computational modelling and innovative cell biology, I propose an updated model of lipid rafts that readily accommodates diverse views on plasma-membrane micro-organization.A widely accepted hypothesis in contemporary cell biology is that freely diffusing, stable, lateral assemblies of sphingolipids and cholesterol, which are termed lipid rafts 1-3 , constitute an important organizing principle for the plasma membrane. The basic concept is that lipid rafts can facilitate selective protein-protein interactions by selectively excluding or including proteins. This lipid-based sorting mechanism has been widely implicated in the assembly of transient signalling platforms and more permanent structures such as the immunological synapse, as well as in the sorting of proteins for entry into specific exocytic and endocytic trafficking pathways [1][2][3] . Despite the undoubted theoretical utility of lipid rafts to many cell biological processes, the basic hypothesis that stable lipid rafts exist at all in biological membranes is under intense scrutiny 4,5 . This is partly because lipid rafts, if they exist in resting cell membranes, are too small to be resolved by fluorescent microscopy and have no defined ultrastructure; therefore, proving their existence is problematic. This article will consider the biophysical properties of model membranes that underpin the lipid raft hypothesis, and the limitations of the biochemical approaches that have been used to study rafts in biological membranes that largely account for the current debate on the hypothesis mentioned above. After examining the challenges that are involved in correlating observations, which have been made in model and cellular membranes, I focus on synthesizing recent data on the size of lipid domains in model membranes with observations that have been obtained by imaging intact plasma membranes. These imaging approaches include single particle tracking (SPT), single fluorophore video tracking (SFVT), fluorescence resonance energy transfer (FRET), homo-FRET and electron microscopy (EM). On the one hand, these studies challenge the simplistic null hypothesis that lipid-based assemblies, such as lipid rafts, do not exist in biological membranes. On the other hand, it is timely to reconsider the raft hypothesis in the light of these new data because the consensus model that emerges is more complex than a simplistic notion of stable, freely diffusing lipid rafts. Some intriguing new questions aboutCompeting interests statement The author declares no competing financial interests. DATABASES

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“…Their partitioning into L o phase is favored by the fact that sphingolipids can create a complex network of hydrogen bonds due to the presence of the amide nitrogen, the carbonyl oxygen, and the hydroxyl group positioned in proximity to the water/lipid interface of the bilayer (118). Moreover, the hydrogen bond network between lipids stabilizes a more rigid phase in the bilayer and increases order (119,120). Plant GIPC long chain base profiles are dominated by t18:0 and t18:1 species in widely varying proportions (t representing trihydroxylated, called phytosphingosine; 0 or 1 for no or one insaturation; for a review, see Ref.…”

Section: Free and Conjugated Phytosterols Exhibit Various Abilities Tmentioning

confidence: 99%

Differential Effect of Plant Lipids on Membrane Organization

Grosjean

Mongrand

Beney

et al. 2015

Journal of Biological Chemistry

104

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Background: The effect of the wide variety of plant lipids on membrane organization is still poorly understood. Results: The local amounts of phytosphingolipids and free and conjugated phytosterols control the relative proportion and spatial distribution of ordered domains. Conclusion: Plant lipids differently modulate, alone or in combination, membrane heterogeneity. Significance: Our results highlight how plant lipid diversity might drive the plasma membrane subcompartmentalization.

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Sphingomyelin-Cholesterol Domains in Phospholipid Membranes: Atomistic Simulation

Cited by 168 publications

References 63 publications

Molecular Dynamics Simulations of Ternary Membrane Mixture: Phosphatidylcholine, Phosphatidic Acid, and Cholesterol

Molecular Dynamics Simulations of Ternary Membrane Mixture: Phosphatidylcholine, Phosphatidic Acid, and Cholesterol

Lipid rafts: contentious only from simplistic standpoints

Differential Effect of Plant Lipids on Membrane Organization

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