Role of sterol type on lateral pressure profiles of lipid membranes affecting membrane protein functionality: Comparison between cholesterol, desmosterol, 7-dehydrocholesterol and ketosterol

Ollila, O. H. Samuli; Róg, Tomasz; Karttunen, Mikko; Vattulainen, Ilpo

doi:10.1016/j.jsb.2007.01.012

Cited by 115 publications

(61 citation statements)

References 75 publications

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“…In fact, the single experimental investigation of the DOPC pressure profile reported to date only provides qualitative data for part of the tail region [114]. A DOPC pressure profile was published for an atomistic model [97]; that profile is somewhat different from ours, especially in the tails region. While atomistic models are generally expected to be more accurate than CG models, in this case there is some evidence to the contrary.…”

Section: Resultsmentioning

confidence: 64%

“…The profiles are presented as “raw data”, that is, no extra processing was done to smooth the curves; moreover, the data are not averaged over the two monolayers. Incidentally, we note that the approach used to calculate intramembrane profiles, which is standard in membrane simulations [76], [97]–[99], relies on the assumption that the bilayer is flat; we will show in the following that the validity of this assumption, especially for large systems, is questionable.…”

Section: Resultsmentioning

confidence: 95%

“…The severity of the resulting artifacts was shown to correlate with the system size. Since the procedures that we employed are standard [76], [97]–[99], the problem highlighted in this paper is expected to generally affect membrane simulations, irrespectively of the specific modeling details. Furthermore, these artifacts are likely to become more severe in the future, because the growing computer power will allow larger membranes to be simulated (in general, increasing the size of simulated systems is desirable, to limit periodicity and finite-size effects).…”

Section: Discussionmentioning

confidence: 99%

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The ELBA Force Field for Coarse-Grain Modeling of Lipid Membranes

2011

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A new coarse-grain model for molecular dynamics simulation of lipid membranes is presented. Following a simple and conventional approach, lipid molecules are modeled by spherical sites, each representing a group of several atoms. In contrast to common coarse-grain methods, two original (interdependent) features are here adopted. First, the main electrostatics are modeled explicitly by charges and dipoles, which interact realistically through a relative dielectric constant of unity (). Second, water molecules are represented individually through a new parametrization of the simple Stockmayer potential for polar fluids; each water molecule is therefore described by a single spherical site embedded with a point dipole. The force field is shown to accurately reproduce the main physical properties of single-species phospholipid bilayers comprising dioleoylphosphatidylcholine (DOPC) and dioleoylphosphatidylethanolamine (DOPE) in the liquid crystal phase, as well as distearoylphosphatidylcholine (DSPC) in the liquid crystal and gel phases. Insights are presented into fundamental properties and phenomena that can be difficult or impossible to study with alternative computational or experimental methods. For example, we investigate the internal pressure distribution, dipole potential, lipid diffusion, and spontaneous self-assembly. Simulations lasting up to 1.5 microseconds were conducted for systems of different sizes (128, 512 and 1058 lipids); this also allowed us to identify size-dependent artifacts that are expected to affect membrane simulations in general. Future extensions and applications are discussed, particularly in relation to the methodology's inherent multiscale capabilities.

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Section: Resultsmentioning

confidence: 64%

Section: Resultsmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

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The ELBA Force Field for Coarse-Grain Modeling of Lipid Membranes

2011

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“…21,22 Although experimental studies quantifying lateral pressure within real membranes are limited, 23 molecular dynamics simulations have shown a lipid composition dependence in the lateral pressure profile. [24][25][26][27] Lipids such as PE form nonlamellar, hexagonal phases in water where the monolayers curve towards water. This contrasts with the flat monolayers of low curvature in a bilayer of lamellar lipids such as PC.…”

Section: Introductionmentioning

confidence: 99%

In vitro Unfolding and Refolding of the Small Multidrug Transporter EmrE

Miller

Charalambous

Rotem

et al. 2009

Journal of Molecular Biology

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“…Importantly, as 7-dehydrocholesterol can incorporate into lipid rafts and alters the protein composition within it (Keller et al 2004), at least some of the disturbances seen in SLOS can be due to the altered function of the lipid rafts. The greatly increased level of 7-dehydrocholesterol leads to increased membrane fluidity and decreased intermolecular packing of phospholipids fatty acyl chains (Vainio et al 2006;Rog et al 2007;Samuli Ollila et al 2007). Membrane X-ray diffraction studies suggest that the minor difference between the structure of cholesterol and 7-dehydrocholesterol leads to significant differences in membrane lipid organization and dynamics .…”

Section: Human Conditions With Altered Cholesterol Biosynthesis: Consmentioning

confidence: 99%

Lipid rafts, cholesterol, and the brain

2008

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SummaryLipid rafts are specialized membrane microdomains that serve as organizing centers for assembly of signaling molecules, influence membrane fluidity and trafficking of membrane proteins, and regulate different cellular processes such as neurotransmission and receptor trafficking. In this article, we provide an overview of current methods for studying lipid rafts and models for how lipid rafts might form and function. Next, we propose a potential mechanism for regulating lipid rafts in the brain via local control of cholesterol biosynthesis by neurotrophins and their receptors. Finally, we discuss evidence that altered cholesterol metabolism and/or lipid rafts play a critical role in the pathophysiology of multiple CNS disorders, including Smith-Lemli-Opitz syndrome, Huntington, Alzheimer's, and Niemman-Pick Type C diseases.

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Role of sterol type on lateral pressure profiles of lipid membranes affecting membrane protein functionality: Comparison between cholesterol, desmosterol, 7-dehydrocholesterol and ketosterol

Cited by 115 publications

References 75 publications

The ELBA Force Field for Coarse-Grain Modeling of Lipid Membranes

The ELBA Force Field for Coarse-Grain Modeling of Lipid Membranes

In vitro Unfolding and Refolding of the Small Multidrug Transporter EmrE

Lipid rafts, cholesterol, and the brain

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