Oak Ridge, TN, United States
Oak Ridge, TN, United States

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PubMed | Joint Institute for Neutron science, Oak Ridge National Laboratory and Jülich Research Center
Type: Journal Article | Journal: Journal of the American Chemical Society | Year: 2015

The lipid raft hypothesis presents insights into how the cell membrane organizes proteins and lipids to accomplish its many vital functions. Yet basic questions remain about the physical mechanisms that lead to the formation, stability, and size of lipid rafts. As a result, much interest has been generated in the study of systems that contain similar lateral heterogeneities, or domains. In the current work we present an experimental approach that is capable of isolating the bending moduli of lipid domains. This is accomplished using neutron scattering and its unique sensitivity to the isotopes of hydrogen. Combining contrast matching approaches with inelastic neutron scattering, we isolate the bending modulus of 13 nm diameter domains residing in 60 nm unilamellar vesicles, whose lipid composition mimics the mammalian plasma membrane outer leaflet. Importantly, the bending modulus of the nanoscopic domains differs from the modulus of the continuous phase surrounding them. From additional structural measurements and all-atom simulations, we also determine that nanoscopic domains are in-register across the bilayer leaflets. Taken together, these results inform a number of theoretical models of domain/raft formation and highlight the fact that mismatches in bending modulus must be accounted for when explaining the emergence of lateral heterogeneities in lipid systems and biological membranes.

Marquardt D.,Brock University | Kucerka N.,National Research Council Canada | Kucerka N.,Comenius University | Kucerka N.,Joint Institute for Nuclear Research | And 5 more authors.
Langmuir | Year: 2015

To this day, α-tocopherols (aToc) role in humans is not well known. In previous studies, we have tried to connect aTocs biological function with its location in a lipid bilayer. In the present study, we have determined, by means of small-angle neutron diffraction, that not only is aTocs hydroxyl group located high in the membrane but its tail also resides far from the center of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayers. In addition, we located aTocs hydroxyl group above the lipid backbone in 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE), 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-l-serine (POPS), and sphingomyelin bilayers, suggesting that aTocs location near the lipid-water interface may be a universal property of vitamin E. In light of these data, how aToc efficiently terminates lipid hydroperoxy radicals at the membrane center remains an open question. © 2014 American Chemical Society.

Egami T.,Joint Institute for Neutron science | Egami T.,University of Tennessee at Knoxville | Egami T.,Oak Ridge National Laboratory | Egami T.,Tohoku University | And 5 more authors.
Philosophical Magazine | Year: 2012

The aluminum-gold system exhibits various features that suggest high glass formability, such as a deep eutectic, formation of icosahedral clusters in the intermetallic compound near the eutectic minimum and a strongly negative heat of mixing. However, it is very difficult to form a glass with this system. Various issues related to glass formability are discussed using the Al-Au system as a negative test-case. In particular, the atomic level pressure was calculated from first principles for the first time for Al 2Au, AlAu 2 and AlAu 4 intermetallic compounds. The atomic level pressure is very high in these compounds, suggesting frustrated electronic states which destabilize both crystalline and glassy phases. © 2012 Copyright Taylor and Francis Group, LLC.

Marquardt D.,Brock University | Williams J.A.,Indiana University – Purdue University Indianapolis | Kinnun J.J.,Indiana University – Purdue University Indianapolis | Kucerka N.,National Research Council Canada | And 7 more authors.
Journal of the American Chemical Society | Year: 2014

Using data obtained from different physical techniques (i.e., neutron diffraction, NMR and UV spectroscopy), we present evidence which explains some of the conflicting and inexplicable data found in the literature regarding α-tocopherol's (aToc's) behavior in dimyristoyl phosphatidylcholine (di-14:0PC) bilayers. Without exception, the data point to aToc's active chromanol moiety residing deep in the hydrophobic core of di-14:0PC bilayers, a location that is in stark contrast to aToc's location in other PC bilayers. Our result is a clear example of the importance of lipid species diversity in biological membranes and importantly, it suggests that measurements of aToc's oxidation kinetics, and its associated byproducts observed in di-14:0PC bilayers, should be reexamined, this time taking into account its noncanonical location in this bilayer. © 2013 American Chemical Society.

Heftberger P.,University of Graz | Kollmitzer B.,University of Graz | Heberle F.A.,Oak Ridge National Laboratory | Pan J.,Oak Ridge National Laboratory | And 10 more authors.
Journal of Applied Crystallography | Year: 2014

The highly successful scattering density profile (SDP) model, used to jointly analyze small-angle X-ray and neutron scattering data from unilamellar vesicles, has been adapted for use with data from fully hydrated, liquid crystalline multilamellar vesicles (MLVs). Using a genetic algorithm, this new method is capable of providing high-resolution structural information, as well as determining bilayer elastic bending fluctuations from standalone X-ray data. Structural parameters such as bilayer thickness and area per lipid were determined for a series of saturated and unsaturated lipids, as well as binary mixtures with cholesterol. The results are in good agreement with previously reported SDP data, which used both neutron and X-ray data. The inclusion of deuterated and non-deuterated MLV neutron data in the analysis improved the lipid backbone information but did not improve, within experimental error, the structural data regarding bilayer thickness and area per lipid. © 2014 International Union of Crystallography.

Marquardt D.,University of Graz | Kucerka N.,Joint Institute for Nuclear Research | Kucerka N.,Comenius University | Wassall S.R.,Indiana University – Purdue University Indianapolis | And 5 more authors.
Chemistry and Physics of Lipids | Year: 2016

It is well known that cholesterol modifies the physical properties of lipid bilayers. For example, the much studied liquid-ordered L o phase contains rapidly diffusing lipids with their acyl chains in the all trans configuration, similar to gel phase bilayers. Moreover, the L o phase is commonly associated with cholesterol-enriched lipid rafts, which are thought to serve as platforms for signaling proteins in the plasma membrane. Cholesterol's location in lipid bilayers has been studied extensively, and it has been shown - at least in some bilayers - to align differently from its canonical upright orientation, where its hydroxyl group is in the vicinity of the lipid-water interface. In this article we review recent works describing cholesterol's location in different model membrane systems with emphasis on results obtained from scattering, spectroscopic and molecular dynamics studies. © 2016 Elsevier Ireland Ltd.

Heberle F.A.,Oak Ridge National Laboratory | Doktorova M.,Cornell University | Goh S.L.,Cornell University | Standaert R.F.,Oak Ridge National Laboratory | And 6 more authors.
Journal of the American Chemical Society | Year: 2013

Nanometer-scale domains in cholesterol-rich model membranes emulate lipid rafts in cell plasma membranes (PMs). The physicochemical mechanisms that maintain a finite, small domain size are, however, not well understood. A special role has been postulated for chain-asymmetric or hybrid lipids having a saturated sn-1 chain and an unsaturated sn-2 chain. Hybrid lipids generate nanodomains in some model membranes and are also abundant in the PM. It was proposed that they align in a preferred orientation at the boundary of ordered and disordered phases, lowering the interfacial energy and thus reducing domain size. We used small-angle neutron scattering and fluorescence techniques to detect nanoscopic and modulated liquid phase domains in a mixture composed entirely of nonhybrid lipids and cholesterol. Our results are indistinguishable from those obtained previously for mixtures containing hybrid lipids, conclusively showing that hybrid lipids are not required for the formation of nanoscopic liquid domains and strongly implying a common mechanism for the overall control of raft size and morphology. We discuss implications of these findings for theoretical descriptions of nanodomains. © 2013 American Chemical Society.

Egami T.,Joint Institute for Neutron science | Egami T.,University of Tennessee at Knoxville | Egami T.,Oak Ridge National Laboratory
JOM | Year: 2010

Liquids and glasses have been well known to human kind for millennia. And yet major mysteries remain in the behavior of glasses and liquids at the atomic level, and identifying the microscopic mechanisms that control the properties of glasses is one of the most challenging unsolved problems in physical sciences. For this reason, applying simplistic approaches to explain the behavior of metallic glasses can lead to serious errors. On the other hand because metallic glasses are atomic glasses with relatively simple structure, they may offer better opportunities to advance our fundamental understanding on the nature of the glass. The difficulties inherent to the problem and some recent advances are reviewed here. © 2010 TMS.

Marquardt D.,Brock University | Williams J.A.,Indiana University – Purdue University Indianapolis | Kucerka N.,National Research Council Canada | Atkinson J.,Brock University | And 6 more authors.
Journal of the American Chemical Society | Year: 2013

We show evidence of an antioxidant mechanism for vitamin E which correlates strongly with its physical location in a model lipid bilayer. These data address the overlooked problem of the physical distance between the vitamin's reducing hydrogen and lipid acyl chain radicals. Our combined data from neutron diffraction, NMR, and UV spectroscopy experiments all suggest that reduction of reactive oxygen species and lipid radicals occurs specifically at the membrane's hydrophobic-hydrophilic interface. The latter is possible when the acyl chain "snorkels" to the interface from the hydrocarbon matrix. Moreover, not all model lipids are equal in this regard, as indicated by the small differences in vitamin's location. The present result is a clear example of the importance of lipid diversity in controlling the dynamic structural properties of biological membranes. Importantly, our results suggest that measurements of aToc oxidation kinetics, and its products, should be revisited by taking into consideration the physical properties of the membrane in which the vitamin resides. © 2013 American Chemical Society.

Armstrong C.L.,McMaster University | Haussler W.,TU Munich | Seydel T.,Laue Langevin Institute | Katsaras J.,Oak Ridge National Laboratory | And 4 more authors.
Soft Matter | Year: 2014

Lipid dynamics in the cholesterol-rich (40 mol%) liquid-ordered (l o) phase of dimyristoylphosphatidylcholine membranes were studied using neutron spin-echo and neutron backscattering. Recent theoretical and experimental evidence supports the notion of the liquid-ordered phase in phospholipid membranes as a locally structured liquid, with small ordered 'domains' of a highly dynamic nature in equilibrium with a disordered matrix [S. Meinhardt, R. L. C. Vink and F. Schmid, Proc. Natl. Acad. Sci. U. S. A., 2013, 110(12), 4476-4481, C. L. Armstrong et al., PLoS One, 2013, 8(6), e66162]. This local structure was found to have a pronounced impact on the membranes' dynamical properties. We found that the long-wavelength dynamics in the liquid-ordered phase, associated with the elastic properties of the membranes, were faster by two orders of magnitude as compared to the liquid disordered phase. At the same time, collective nanoscale diffusion was significantly slower. The presence of a soft-mode (a slowing down) in the long-wavelength dispersion relationship suggests an upper size limit for the ordered lipid domain of ≈220 Å. Moreover, from the relaxation rate of the collective lipid diffusion of lipid-lipid distances, the lifetime of these domains was estimated to be about 100 nanoseconds. © 2014 the Partner Organisations.

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