The Experts below are selected from a list of 159 Experts worldwide ranked by ideXlab platform
John F. Nagle - One of the best experts on this subject based on the ideXlab platform.
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experimental support for tilt dependent theory of biomembrane mechanics
Physical Review Letters, 2014Co-Authors: Michael S Jablin, Kiyotaka Akabori, John F. NagleAbstract:Recent simulations have indicated that the traditional model for topographical fluctuations in biomembranes should be enriched to include molecular tilt. Here we report the first experimental data supporting this enrichment. Utilizing a previously posited tilt-dependent model, a height-height correlation function was derived. The x-ray scattering from a liquid crystalline stack of oriented fluid Phase Lipid bilayers was calculated and compared with experiment. By fitting the measured scattering intensity, both the bending modulus ${K}_{c}=8.3\ifmmode\pm\else\textpm\fi{}0.6\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}20}\text{ }\text{ }\mathrm{J}$ and the tilt modulus ${K}_{\ensuremath{\theta}}=95\ifmmode\pm\else\textpm\fi{}7\text{ }\text{ }\mathrm{mN}/\mathrm{m}$ were determined for DOPC Lipid bilayers at $30\text{ }\ifmmode^\circ\else\textdegree\fi{}\mathrm{C}$.
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Structure of Fully Hydrated Fluid Phase Lipid Bilayers with Monounsaturated Chains
The Journal of Membrane Biology, 2006Co-Authors: Norbert Kučerka, Stephanie Tristram-nagle, John F. NagleAbstract:Quantitative structures are obtained at 30°C for the fully hydrated fluid Phases of palmitoyloleoylphosphatidylcholine (POPC), with a double bond on the sn -2 hydrocarbon chain, and for dierucoylphosphatidylcholine (di22:1PC), with a double bond on each hydrocarbon chain. The form factors F ( q _ z ) for both Lipids are obtained using a combination of three methods. (1) Volumetric measurements provide F (0). (2) X-ray scattering from extruded unilamellar vesicles provides Ι F ( q _ z )Ι for low q _ z . (3) Diffuse X-ray scattering from oriented stacks of bilayers provides Ι F ( q _ z )Ι for high q _ z . Also, data using method (2) are added to our recent data for dioleoylphosphatidylcholine (DOPC) using methods (1) and (3); the new DOPC data agree very well with the recent data and with (4) our older data obtained using a liquid crystallographic X-ray method. We used hybrid electron density models to obtain structural results from these form factors. The result for area per Lipid ( A ) for DOPC 72.4 ± 0.5 Å^2 agrees well with our earlier publications, and we find A = 69.3 ± 0.5 Å^2 for di22:1PC and A = 68.3 ± 1.5 Å^2 for POPC. We obtain the values for five different average thicknesses: hydrophobic, steric, head-head, phosphate-phosphate and Luzzati. Comparison of the results for these three Lipids and for our recent dimyristoylphosphatidylcholine (DMPC) determination provides quantitative measures of the effect of unsaturation on bilayer structure. Our results suggest that Lipids with one monounsaturated chain have quantitative bilayer structures closer to Lipids with two monounsaturated chains than to Lipids with two completely saturated chains.
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structure of Lipid bilayers
Biochimica et Biophysica Acta, 2000Co-Authors: John F. Nagle, Stephanie TristramnagleAbstract:The quantitative experimental uncertainty in the structure of fully hydrated, biologically relevant, fluid (Lα) Phase Lipid bilayers has been too large to provide a firm base for applications or for comparison with simulations. Many structural methods are reviewed including modern liquid crystallography of Lipid bilayers that deals with the fully developed undulation fluctuations that occur in the Lα Phase. These fluctuations degrade the higher order diffraction data in a way that, if unrecognized, leads to erroneous conclusions regarding bilayer structure. Diffraction measurements at high instrumental resolution provide a measure of these fluctuations. In addition to providing better structural determination, this opens a new window on interactions between bilayers, so the experimental determination of interbilayer interaction parameters is reviewed briefly. We introduce a new structural correction based on fluctuations that has not been included in any previous studies. Updated measurements, such as for the area compressibility modulus, are used to provide adjustments to many of the literature values of structural quantities. Since the gel (Lβ′) Phase is valuable as a stepping stone for obtaining fluid Phase results, a brief review is given of the lower temperature Phases. The uncertainty in structural results for Lipid bilayers is being reduced and best current values are provided for bilayers of five Lipids.
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x ray structure determination of fully hydrated l alpha Phase dipalmitoylphosphatidylcholine bilayers
Biophysical Journal, 1996Co-Authors: John F. Nagle, Horia I Petrache, Stephanie Tristramnagle, R. Zhang, R M SuterAbstract:Bilayer form factors obtained from x-ray scattering data taken with high instrumental resolution are reported for multilamellar vesicles of L alpha Phase Lipid bilayers of dipalmitoylphosphatidylcholine at 50 degrees C under varying osmotic pressure. Artifacts in the magnitudes of the form factors due to liquid crystalline fluctuations have been eliminated by using modified Caille theory. The Caille fluctuation parameter eta 1 increases systematically with increasing lamellar D spacing and this explains why some higher order peaks are unobservable for the larger D spacings. The corrected form factors fall on one smooth continuous transform F(q); this shows that the bilayer does not change shape as D decreases from 67.2 A (fully hydrated) to 60.9 A. The distance between headgroup peaks is obtained from Fourier reconstruction of samples with four orders of diffraction and from electron density models that use 38 independent form factors. By combining these results with previous gel Phase results, area AF per Lipid molecule and other structural quantities are obtained for the fluid L alpha Phase. Comparison with results that we derived from previous neutron diffraction data is excellent, and we conclude from diffraction studies that AF = 62.9 +/- 1.3 A2, which is in excellent agreement with a previous estimate from NMR data.
Timothy A Cross - One of the best experts on this subject based on the ideXlab platform.
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validation of the single stranded channel conformation of gramicidin a by solid state nmr
Proceedings of the National Academy of Sciences of the United States of America, 1999Co-Authors: F A Kovacs, Jack R. Quine, Timothy A CrossAbstract:Abstract The monovalent cation selective channel formed by a dimer of the polypeptide gramicidin A has a single-stranded, right-handed helical motif with 6.5 residues per turn forming a 4-A diameter pore. The structure has been refined to high resolution against 120 orientational constraints obtained from samples in a liquid-crystalline Phase Lipid bilayer. These structural constraints from solid-state NMR reflect the orientation of spin interaction tensors with respect to a unique molecular axis. Because these tensors are fixed in the molecular frame and because the samples are uniformly aligned with respect to the magnetic field of the NMR spectrometer, each constraint restricts the orientation of internuclear vectors with respect to the laboratory frame of reference. The structural motif of this channel has been validated, and the high-resolution structure has led to precise models for cation binding, cation selectivity, and cation conductance efficiency. The structure is consistent with the electrophysiological data and numerous biophysical studies. Contrary to a recent claim [Burkhart, B. M., Li, N., Langs, D. A., Pangborn, W. A. & Duax, W. L. (1998) Proc. Natl. Acad. Sci. USA 95, 12950–12955], the solid-state NMR constraints for gramicidin A in a Lipid bilayer are not consistent with an x-ray crystallographic structure for gramicidin having a double-stranded, right-handed helix with 7.2 residues per turn.
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High-resolution polypeptide structure in a lamellar Phase Lipid environment from solid state NMR derived orientational constraints
Structure, 1997Co-Authors: Randal R Ketchem, Brigitte Le Roux, Timothy A CrossAbstract:Background: Solid-state nuclear magnetic resonance (NMR) spectroscopy provides novel structural constraints from uniformly aligned samples. These orientational constraints orient specific atomic sites with respect to the magnetic field direction and the unique molecular axis of alignment. Solid-state NMR is uniquely and ideally suited for providing such structural constraints on polypeptides and proteins in a lamellar Phase Lipid environment. Membrane protein structure represents a great challenge for structural biologists; a new approach for characterizing high resolution three-dimensional structure in such an environment is needed. Results: The optimal use of orientational constraints for defining three-dimensional structures is demonstrated with the elucidation of the gramicidin A channel structure at high resolution. Initial structures are refined against both the experimental constraints and the CHARMM energy using a novel simulated-annealing protocol to define torsion angle solutions with an error bar of approximately ± 5°. Conclusions: This analysis results in the determination of a high-resolution, time averaged structure of gramicidin A obtained in a Lipid bilayer environment above the gel-to-liquid crystalline Phase transition temperature. It is demonstrated that solid-state NMR can be used to establish polypeptide, and potentially protein, structures in such an environment. Furthermore, this high-resolution structure is demonstrated to provide new insights into polypeptide function. For the gramicidin A channel the roles of the indole groups that facilitate ion transport and details of the cation solvation environment provided by the amide oxygens are characterized.
Stephanie Tristramnagle - One of the best experts on this subject based on the ideXlab platform.
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x ray structure thermodynamics elastic properties and md simulations of cardiolipin dimyristoylphosphatidylcholine mixed membranes
Chemistry and Physics of Lipids, 2014Co-Authors: Alexander L Boscia, Bradley W Treece, Dariush Mohammadyani, Judith Kleinseetharaman, Anthony R Braun, Tsjerk A Wassenaar, Beate Klosgen, Stephanie TristramnagleAbstract:Cardiolipins (CLs) are important biologically for their unique role in biomembranes that couple phosphorylation and electron transport like bacterial plasma membranes, chromatophores, chloroplasts and mitochondria. CLs are often tightly coupled to proteins involved in oxidative phosphorylation. The first step in understanding the interaction of CL with proteins is to obtain the pure CL structure, and the structure of mixtures of CL with other Lipids. In this work we use a variety of techniques to characterize the fluid Phase structure, material properties and thermodynamics of mixtures of dimyristoylphosphatidylcholine (DMPC) with tetramyristoylcardiolipin (TMCL), both with 14-carbon chains, at several mole percentages. X-ray diffuse scattering was used to determine structure, including bilayer thickness and area/Lipid, the bending modulus, KC, and SXray, a measure of chain orientational order. Our results reveal that TMCL thickens DMPC bilayers at all mole percentages, with a total increase of ∼6 A in pure TMCL, and increases AL from 64 A2 (DMPC at 35 °C) to 109 A2 (TMCL at 50 °C). KC increases by ∼50%, indicating that TMCL stiffens DMPC membranes. TMCL also orders DMPC chains by a factor of ∼2 for pure TMCL. Coarse grain molecular dynamics simulations confirm the experimental thickening of 2 A for 20 mol% TMCL and locate the TMCL headgroups near the glycerol-carbonyl region of DMPC; i.e., they are sequestered below the DMPC phosphocholine headgroup. Our results suggest that TMCL plays a role similar to cholesterol in that it thickens and stiffens DMPC membranes, orders chains, and is positioned under the umbrella of the PC headgroup. CL may be necessary for hydrophobic matching to inner mitochondrial membrane proteins. Differential scanning calorimetry, SXray and CGMD simulations all suggest that TMCL does not form domains within the DMPC bilayers. We also determined the gel Phase structure of TMCL, which surprisingly displays diffuse X-ray scattering, like a fluid Phase Lipid. AL = 40.8 A2 for the ½TMCL gel Phase, smaller than the DMPC gel Phase with AL = 47.2 A2, but similar to AL of DLPE = 41 A2, consistent with untilted chains in gel Phase TMCL.
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structure of Lipid bilayers
Biochimica et Biophysica Acta, 2000Co-Authors: John F. Nagle, Stephanie TristramnagleAbstract:The quantitative experimental uncertainty in the structure of fully hydrated, biologically relevant, fluid (Lα) Phase Lipid bilayers has been too large to provide a firm base for applications or for comparison with simulations. Many structural methods are reviewed including modern liquid crystallography of Lipid bilayers that deals with the fully developed undulation fluctuations that occur in the Lα Phase. These fluctuations degrade the higher order diffraction data in a way that, if unrecognized, leads to erroneous conclusions regarding bilayer structure. Diffraction measurements at high instrumental resolution provide a measure of these fluctuations. In addition to providing better structural determination, this opens a new window on interactions between bilayers, so the experimental determination of interbilayer interaction parameters is reviewed briefly. We introduce a new structural correction based on fluctuations that has not been included in any previous studies. Updated measurements, such as for the area compressibility modulus, are used to provide adjustments to many of the literature values of structural quantities. Since the gel (Lβ′) Phase is valuable as a stepping stone for obtaining fluid Phase results, a brief review is given of the lower temperature Phases. The uncertainty in structural results for Lipid bilayers is being reduced and best current values are provided for bilayers of five Lipids.
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x ray structure determination of fully hydrated l alpha Phase dipalmitoylphosphatidylcholine bilayers
Biophysical Journal, 1996Co-Authors: John F. Nagle, Horia I Petrache, Stephanie Tristramnagle, R. Zhang, R M SuterAbstract:Bilayer form factors obtained from x-ray scattering data taken with high instrumental resolution are reported for multilamellar vesicles of L alpha Phase Lipid bilayers of dipalmitoylphosphatidylcholine at 50 degrees C under varying osmotic pressure. Artifacts in the magnitudes of the form factors due to liquid crystalline fluctuations have been eliminated by using modified Caille theory. The Caille fluctuation parameter eta 1 increases systematically with increasing lamellar D spacing and this explains why some higher order peaks are unobservable for the larger D spacings. The corrected form factors fall on one smooth continuous transform F(q); this shows that the bilayer does not change shape as D decreases from 67.2 A (fully hydrated) to 60.9 A. The distance between headgroup peaks is obtained from Fourier reconstruction of samples with four orders of diffraction and from electron density models that use 38 independent form factors. By combining these results with previous gel Phase results, area AF per Lipid molecule and other structural quantities are obtained for the fluid L alpha Phase. Comparison with results that we derived from previous neutron diffraction data is excellent, and we conclude from diffraction studies that AF = 62.9 +/- 1.3 A2, which is in excellent agreement with a previous estimate from NMR data.
Thomas Hellweg - One of the best experts on this subject based on the ideXlab platform.
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aescin induced conversion of gel Phase Lipid membranes into bicelle like Lipid nanoparticles
Langmuir, 2019Co-Authors: Ramsia Geisler, Martin Cramer Pedersen, Yvonne Hannappel, Ralf Schweins, Sylvain Prevost, Rajeev Dattani, Lise Arleth, Thomas HellwegAbstract:: Mixtures of the phosphoLipid 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and the saponin β-aescin spontaneously form monodisperse, bilayered discoidal micelles (also known as "bicelles" or "nanodisks") in aqueous solution. Such bicelles form below the melting temperature of DMPC when the phosphoLipids are in the rigid Lβ' state and are precursors of spontaneously formed vesicles. The aescin concentration must be far above the cmcaescin (≈0.3-0.4 mM). It was found that the shape and size of the bicelles are tunable by composition. High amounts of aescin decrease the size of the bicelles from diameters of ∼300 A at 7 mol % to ∼120 A at 30 mol % β-aescin. The structures are scrutinized by complementary small-angle X-ray and neutron scattering experiments. The scattering curves are subsequently analyzed by a model-independent (indirect Fourier transform analysis) and a model-based approach where bicelles are described as polydisperse bilayer disks encircled by a β-aescin rim. Moreover, the monomodal distribution and low polydispersity of the samples were confirmed by photon correlation spectroscopy. The discoidal structures were visualized by transmission electron microscopy.
Kyoichi Mizuno - One of the best experts on this subject based on the ideXlab platform.
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appearance of Lipid laden intima and neovascularization after implantation of bare metal stents extended late Phase observation by intracoronary optical coherence tomography
Journal of the American College of Cardiology, 2009Co-Authors: Masamichi Takano, Masanori Yamamoto, Shigenobu Inami, Daisuke Murakami, Takayoshi Ohba, Yoshihiko Seino, Kyoichi MizunoAbstract:Objectives We examined the neointimal characteristics of bare-metal stents (BMS) in extended late Phase by the use of optical coherence tomography (OCT). Background The long-term neointimal features after BMS implantation have not yet been fully characterized. Methods Intracoronary OCT observation of BMS segments was performed during the early Phase ( Results Normal neointima proliferated homogeneously, and Lipid-laden intima was not observed in the early Phase. In the late Phase, Lipid-laden intima, intimal disruption, and thrombus frequently were found in comparison with the early Phase (67% vs. 0%, 38% vs. 0%, and 52% vs. 5%, respectively; p Conclusions This OCT study suggests that neointima within the BMS often transforms into Lipid-laden tissue during an extended period of time and that expansion of neovascularization from peristent to intraintima contributes to atherosclerotic progression of neointima.