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  • 1. Adebahr, J
    et al.
    Forsyth, M
    Gavelin, P
    Jacobsson, P
    Orädd, Greger
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Ion and Solvent Dynamics in Gel Electrolytes Based on Ethylene Oxide Grafted Acrylate Polymers2002Ingår i: The Journal of Physical Chemistry B, Vol. 106, nr 47, s. 12119-12123Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Multinuclear pulsed field gradient NMR measurements and rheological viscosity measurements were performed on three series of polymer gel electrolytes. The gels were based on a lithium salt electrolyte swollen into a copolymer matrix comprising an acrylate backbone and ethylene oxide side chains. In each series the side chains differed in length and number, but the acrylate-to-ethylene oxide ratio was kept constant. It was found that the self-diffusion coefficient of the cations was much lower than that of the anions, and that it decreased rapidly when the side chains got longer. In contrast, the self-diffusion coefficient of the anions was found to be independent of chain length. In the gel electrolytes, the diffusion coefficients of the solvent molecules are relatively constant despite an increased viscosity with increasing length of the side chains. However, in salt-free gels made for comparison, the diffusion coefficients of the solvent molecules decreased with increasing length of the side chains, which is consistent with an increased viscosity.

  • 2.
    Andersson, Gustav
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Orädd, Greger
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Umeå Centre for Comparative Biology (UCCB).
    Sultan, Fahad
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Novikov, Lev N.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    In vivo Diffusion Tensor Imaging, Diffusion Kurtosis Imaging, and Tractography of a Sciatic Nerve Injury Model in Rat at 9.4T2018Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, artikel-id 12911Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Peripheral nerve injuries result in severe loss of sensory and motor functions in the afflicted limb. There is a lack of standardised models to non-invasively study degeneration, regeneration, and normalisation of neuronal microstructure in peripheral nerves. This study aimed to develop a non-invasive evaluation of peripheral nerve injuries, using diffusion tensor imaging (DTI), diffusion kurtosis imaging (DKI), and tractography on a rat model of sciatic nerve injury. 10 female Sprague Dawley rats were exposed to sciatic nerve neurotmesis and studied using a 9.4 T magnet, by performing DTI and DKI of the sciatic nerve before and 4 weeks after injury. The distal nerve stump showed a decrease in fractional anisotropy (FA), mean kurtosis (MK), axonal water fraction (AWF), and radial and axonal kurtosis (RK, AK) after injury. The proximal stump showed a significant decrease in axial diffusivity (AD) and increase of MK and AK as compared with the uninjured nerve. Both mean diffusivity (MD) and radial diffusivity (RD) increased in the distal stump after injury. Tractography visualised the sciatic nerve and the site of injury, as well as local variations of the diffusion parameters following injury. In summary, the described method detects changes both proximal and distal to the nerve injury.

  • 3.
    Chermenina, Maria
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Histologi med cellbiologi.
    Schouten, P
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Histologi med cellbiologi.
    Nevalainen, Nina
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Johansson, F
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Histologi med cellbiologi.
    Orädd, Greger
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Strömberg, Ingrid
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Histologi med cellbiologi.
    GDNF is important for striatal organization and maintenance of dopamine neurons grown in the presence of the striatum2014Ingår i: Neuroscience, ISSN 0306-4522, E-ISSN 1873-7544, Vol. 270, s. 1-11Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Glial cell-derived neurotrophic factor (GDNF) exerts neuroprotective and neurorestorative effects on neurons and GDNF plays a significant role in maintenance of the dopamine neurons utilizing grafting to create a nigrostriatal microcircuit of Gdnf knockout (Gdnf(-/-)) tissue. To further evaluate the role of GDNF on organization of the nigrostriatal system, single or double grafts of ventral mesencephalon (VM) and lateral ganglionic eminence (LGE) with mismatches in Gdnf genotypes were performed. The survival of single grafts was monitored utilizing magnetic resonance imaging (MRI) and cell survival and graft organization were evaluated with immunohistochemistry. The results revealed that the size of VM single grafts did not change over time independent of genotype, while the size of the LGE transplants was significantly reduced already at 2weeks postgrafting when lacking GDNF. Lack of GDNF did not significantly affect the survival of tyrosine hydroxylase (TH)-positive neurons in single VM grafts. However, the survival of TH-positive neurons was significantly reduced in VM derived from Gdnf(+/+) when co-grafted with LGE from the Gdnf(-/-) tissue. In contrast, lack of GDNF in the VM portion of co-grafts had no effect on the survival of TH-positive neurons when co-grafted with LGE from Gdnf(+/+) mice. The TH-positive innervation of co-grafts was sparse when the striatal co-grafts were derived from the Gdnf(-/-) tissue while dense and patchy when innervating LGE producing GDNF. The TH-positive innervation overlapped with the organization of dopamine and cyclic AMP-regulated phosphoprotein-relative molecular mass 32,000 (DARPP-32)-positive neurons, that was disorganized in LGE lacking GDNF production. In conclusion, GDNF is important for a proper striatal organization and for survival of TH-positive neurons in the presence of the striatal tissue.

  • 4. Danino, Dganit
    et al.
    Weihs, Daphne
    Zana, Raoul
    Orädd, Greger
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Lindblom, Göran
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Abe, Masahiko
    Talmon, Yeshayahu
    Microstructures in the aqueous solutions of a hybrid anionic fluorocarbon/hydrocarbon surfactant2003Ingår i: Journal of Colloid and Interface Science, Vol. 259, nr 2, s. 382-90Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The aqueous solutions of the anionic hybrid fluorocarbon/hydrocarbon surfactant sodium 1-oxo-1[4-(tridecafluorohexyl)phenyl]-2-hexanesulfate (FC6HC4) shows peculiar rheological behavior. At 25 °C the viscosity vs concentration curve goes successively through a maximum and a minimum, while the viscosity vs temperature curve of the 10 wt% aqueous FC6HC4 solution goes through a marked maximum at 36 °C [Tobita et al., Langmuir 13 (1997) 5054]. In an attempt to explain these properties the microstructure of aqueous solutions of FC6HC4 has been investigated by means of digital light microscopy, transmission electron microscopy at cryogenic temperature (cryo-TEM), rheology, and self-diffusion NMR. At 20 °C, the increase of the FC6HC4 concentration was found to result in a progressive change of structure of the surfactant assemblies from mainly spherical micelles at 0.5 wt% to mainly cylindrical micelles at 10 wt%. At intermediate concentrations small disklike micelles and small complete and incomplete vesicles coexisting with cylindrical micelles were visualized. The occurrence of stretched cylindrical micelles is responsible for the effect of the surfactant concentration on the solution viscosity. Cryo-TEM, rheology, and self-diffusion NMR all suggest that an increase of the temperature brings about a growth of the assemblies present in the 10 wt% solution of FC6HC4. The structure of the assemblies present at the temperature where the viscosity is a maximum could not be elucidated by cryo-TEM because of the probable occurrence of an on-the-grid phase transformation, the result of blotting during specimen preparation. Nevertheless, the results show that the observed large assemblies break up at higher temperature to give rise to a more labile bicontinuous structure that consists of multiconnected disordered lamellae, with many folds and creases, and that may well be the L3 phase.

  • 5. de la Serna, Jorge Bernardino
    et al.
    Orädd, Greger
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Bagatolli, Luis A
    Simonsen, Adam C
    Marsh, Derek
    Lindblom, Göran
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Perez-Gil, Jesus
    Segregated Phases in Pulmonary Surfactant Membranes Do Not Show Coexistence of Lipid Populations with Differentiated Dynamic Properties2009Ingår i: Biophysical Journal, Vol. 97, nr 5, s. 1381-1389Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The composition of pulmonary surfactant membranes and films has evolved to support a complex lateral structure, including segregation of ordered/disordered phases maintained up to physiological temperatures. In this study, we have analyzed the temperature-dependent dynamic properties of native surfactant membranes and membranes reconstituted from two surfactant hydrophobic fractions (i.e., all the lipids plus the hydrophobic proteins SP-B and SP-C, or only the total lipid fraction). These preparations show micrometer-sized fluid ordered/disordered phase coexistence, associated with a broad endothermic transition ending close to 37°C. However, both types of membrane exhibit uniform lipid mobility when analyzed by electron paramagnetic resonance with different spin-labeled phospholipids. A similar feature is observed with pulse-field gradient NMR experiments on oriented membranes reconstituted from the two types of surfactant hydrophobic extract. These latter results suggest that lipid dynamics are similar in the coexisting fluid phases observed by fluorescence microscopy. Additionally, it is found that surfactant proteins significantly reduce the average intramolecular lipid mobility and translational diffusion of phospholipids in the membranes, and that removal of cholesterol has a profound impact on both the lateral structure and dynamics of surfactant lipid membranes. We believe that the particular lipid composition of surfactant imposes a highly dynamic framework on the membrane structure, as well as maintains a lateral organization that is poised at the edge of critical transitions occurring under physiological conditions.

  • 6.
    Edman, Ludvig
    et al.
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Fysik.
    Ferry, Anders
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Fysik.
    Orädd, Greger
    Kemi.
    Analysis of diffusion in a solid polymer electrolyte in the context of a phase-separated system2002Ingår i: Physical Review E 65, 042803, nr 4, s. 1-4Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The salt and ionic diffusion coefficients of the salt LiN(CF3SO2)2 (LiTFSI) dissolved in high-molecular-weight poly(ethylene oxide) [PEO] have been measured over a broad concentration range, and the interrelationship of the measured values is demonstrated to be in good agreement with basic electrochemical theory. In the light of recently published structural findings, we propose a biphasic model for the conducting amorphous state, consisting of a stoichiometric P(EO)6LiTFSI phase dispersed into a salt-containing disordered phase, and analyze the ionic diffusion data within the framework of the Bruggeman-Landauer theory. The agreement between experimental and fitted data is shown to be excellent. We conclude by pointing out and discussing potential weaknesses of our analysis.

  • 7. Every, HA
    et al.
    Bishop, AG
    MacFarlane, DR
    Orädd, Greger
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Forsyth, M
    Transport properties in a family of dialkylimidazolium ionic liquids2004Ingår i: PHYSICAL CHEMISTRY CHEMICAL PHYSICS, ISSN 1463-9076, Vol. 6, nr 8, s. 1758-65Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The transport properties of 1,3-methylalkylimidazolium based ionic liquids are sensitive to their chemical structure. In this work, two key features of the chemical structure were investigated: the role of the anion and the length of the alkyl chain. Four different anions were examined for the 1,3-methylethylimidazolium salt (MeEtlmX): bromide (Br-), iodide (I-), trifluoromethanesulfonate (Tf-) and bis(trifluoromethanesulfonyt)-amide (NTf2-) anions. Increasing the size of the anion resulted in a decrease of the melting point and a slight increase in the cation diffusion coefficient. The differences in cation diffusion behaviour reflect the differences in viscosity, with much higher viscosities expected for the halide salts. In contrast to this diffusion behaviour, the melt conductivities are all very similar. The inconsistency between the calculated conductivity (based on diffusion measurements) and the conductivity measured, however, is attributed to correlated ion motions and/or the diffusion of neutral species that do not contribute to the conductivity. The effect of the length of the alkyl substituent was also studied for 1,3-methylalkylimidazolium iodide (MeRImI). Increasing the length of the alkyl chain, from methyl to a linear heptyl chain, suppresses the melting point and decreases both the conductivity and cation diffusion coefficients. In this case, the viscosity, as well as the size of the cation, influence ion transport in these materials.

  • 8. Every, Hayley A
    et al.
    Bishop, Andrea G
    MacFarlane, Douglas R
    Orädd, Greger
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Forsyth, Maria
    Room temperature fast-ion conduction in imidazolium halide salts2001Ingår i: Journal of Materials Chemistry Articles, Vol. 11, nr 3031-6Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Fast-ion conduction has been observed in the iodide and bromide salts of 1-methyl-3-ethylimidazolium at ambient temperatures. The melting point of these two compounds is above 350 K and even at 273 K the ionic conductivity in the solid-state is greater than 10–3S cm–1. Cation diffusion coefficients have been measured using fringe field gradient and/or pulse field gradient 1H NMR techniques, which indicated cation diffusion coefficients of the order of 10–10 m2 s–1 in the solid-state. Remarkably, these values are up to an order of magnitude higher than the cation diffusion coefficient in the supercooled liquid at 293 K. The activation energy for diffusion in the solid-state is extremely small, as is typical of solid-state fast-ion conductors and indicates a change in transport mechanism from the melt to the crystal. The inability to detect an 127I signal together with the modelling of the conductivity using the Nernst–Einstein equation suggests that the solid-state conduction is primarily due to cation diffusion. The solid-state fast-ion conduction is most likely related to vacancy diffusion along the cation layers in the crystal. The temperature dependence of the NMR signal intensity indicates that the number of mobile species is increasing with increasing temperature with an activation energy of approximately 20–30 kJ mol–1.

  • 9. Filippov, A V
    et al.
    Rudakova, M A
    Orädd, Greger
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Lindblom, Göran
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Lateral Diffusion of Saturated Phosphatidylcholines in Cholesterol-containing Bilayers2007Ingår i: Biophysics, ISSN 0006-3509, Vol. 52, nr 3, s. 307-14Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A pulsed field gradient NMR was used to study lateral diffusion in the cholesterol-containing oriented bilayers of saturated (dipalmitoyl- and dimyristoyl-) phosphatidylcholines, upon their limiting hydration. Similar dependences of lateral diffusion coefficients on temperature and cholesterol concentration were observed, which agree with phase diagram showing the presence of the regions of disordered and ordered liquid-crystalline phases and a two-phase region. Under the same conditions, the lateral diffusion coefficient of dipalmitoylphosphatidylcholine is lower, which agrees qualitatively with its larger molecular weight. The comparison of data for dipalmitoylphosphatidylcholine with previous results for dipalmitoylsphingomyelin−cholesterol bilayers under the same conditions, in spite of similarity of phase diagrams, shows large (two−three times) differences in the lateral diffusion coefficient and a different profile of its dependence on cholesterol concentration. The comparison of data for dimyristoylphosphatidylcholine with previous results shows that the values of lateral diffusion coefficient and the shape of its dependence on cholesterol concentration coincide at high concentrations (>15 mol%) but differ at lower concentrations The revealed disagreement may be caused by the fact that the measurements were carried out at different water content in the system. At limiting hydration (more than 35% of water), the lateral diffusion coefficient for lipids decreases when cholesterol concentration rises, while at water content about 25% (as a result of equilibrium hydration from vapors) the lateral diffusion coefficient of phosphatidylcholine may be independent of cholesterol concentration. This is the consequence of the denser packing of molecules in the bilayer at reduced water content, an effect that competes with the ordering effect of cholesterol.

  • 10.
    Filippov, Andrey
    et al.
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Orädd, Greger
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Lindblom, Göran
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Domain Formation in Model Membranes Studied by Pulsed-Field Gradient-NMR: The Role of Lipid Polyunsaturation2007Ingår i: Biophysical Journal, Vol. 93, s. 3182-90Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The effects of increased unsaturation in the sn-2 fatty acyl chain of phosphatidylcholines (PCs) on the lipid lateral diffusion have been investigated by pulsed-field gradient NMR. Macroscopically oriented bilayers containing a monosaturated PC, egg sphingomyelin, and cholesterol (CHOL) have been studied at temperatures between 0°C and 60°C, and the number of double bonds in the PC was one, two, four, or six. For PC bilayers, with and without the incorporation of egg sphingomyelin and CHOL, the lateral diffusion increased with increasing number of double bonds, as a consequence of the increased headgroup area caused by the unsaturation. Addition of CHOL caused a decrease in lipid diffusion due to the condensing effect of CHOL on the headgroup area. Phase separation into large domains of liquid-disordered and liquid-ordered phases were observed in the ternary systems with PCs containing four and six double bonds, as evidenced by the occurrence of two lipid diffusion coefficients. PC bilayers with one or two double bonds appear homogeneous on the length scales probed by the experiment, but the temperature dependence of the diffusion suggests that small domains may be present also in these ternary systems.

  • 11.
    Filippov, Andrey
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Orädd, Greger
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Lindblom, Göran
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Effect of NaCl and CaCl2 on the lateral diffusion of zwitterionic and anionic lipids in bilayers2009Ingår i: Chemistry and Physics of Lipids, ISSN 0009-3084, E-ISSN 1873-2941, Vol. 159, nr 2, s. 81-87Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The influence of addition of NaCl or CaCl2 (0.3 M and 0.1 M, respectively) on the lateral diffusion coefficient (DL) of dioleoylphosphatidylcholine (DOPC) or dioleoylphosphatidylglycerol (DOPG) was measured by the pulsed field gradient NMR technique. DL of DOPC was unaffected, whereas the DOPG diffusion decreased with salt concentration. 23Na NMR quadrupole splittings of DOPG between 20 and 60 °C and added NaCl between 0 and 15 wt-% decreased only slightly with salt content, but increased with increasing temperature. Similar results were obtained for palmitoyloleoylphosphatidylglycerol, in which the palmitoyl chain order parameter increased slightly with salt. A model with free and "bound" ions was used to interpret the splitting data.

    With increasing salt content a decrease in the water permeability for DOPG was observed, but not for DOPC, as measured by water diffusion perpendicular to the oriented lipid bilayers.

    It was concluded that calcium and sodium ions interacted with the DOPG head-groups resulting in a decrease in the "free area" per lipid molecule due to a screening of the charged lipid head-groups. Thus, there was a closer packing of DOPG, leading to a decrease in DL and water permeability. DOPC did not show any changes in the bilayer properties upon the addition of ions.

  • 12.
    Filippov, Andrey
    et al.
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Orädd, Greger
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Lindblom, Göran
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Influence of Cholesterol and Water Content on Phospholipid Lateral Diffusion in Bilayers2003Ingår i: Langmuir, Vol. 19, nr 6397-400Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The dependence of lipid lateral diffusion on temperature, cholesterol, and water contents has been studied in oriented bilayers in three phosphatidylcholine lipid systems and one sphingomyelin system. The lateral diffusion of lipids is found to be reduced both by the addition of cholesterol and by decreasing the water content. This reduction can be ascribed to the increase in the ordering of the lipid acyl chains upon cholesterol addition and/or reduced water content. The dependence of the lateral diffusion coefficient on the water content is similar in both the liquid ordered and the liquid disordered phase, while the apparent activation energy for the diffusion process is larger in the liquid ordered phase. We also report an anomalous increase in the lipid diffusion upon small additions of cholesterol to bilayer systems at low water content and temperatures. The increased diffusion is tentatively explained by a reduction of lipid chain entanglements.

  • 13.
    Filippov, Andrey
    et al.
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Orädd, Greger
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Lindblom, Göran
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Lipid Lateral Diffusion in Ordered and Disordered Phases in Raft Mixtures2004Ingår i: Biophysical Journal, Vol. 86, s. 891-6Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Lipid lateral diffusion coefficients in the quarternary system of dioleoylphosphatidylcholine (DOPC), sphingomyelin, cholesterol, and water were determined by the pulsed field gradient NMR technique on macroscopically aligned bilayers. The molar ratio between dioleoylphosphatidylcholine and sphingomyelin was set to 1:1, the cholesterol content was varied between 0 and 45 mol %, the water content was 40 wt %, and the temperature was varied between 293 and 333 K. The diffusion coefficients were separated into fast and slow spectral components by using the CORE method for global analysis of correlated spectral data. A large two-phase region, tentatively assigned to the liquid disordered (ld) and the liquid ordered (lo) phases, was present in the phase diagram. The ld phase was enriched in dioleoylphosphatidylcholine and exhibited diffusion coefficients that were about three to five times larger than for the lo phase. Both the diffusion coefficients and the apparent activation energies for the quarternary systems were compatible with earlier reports on ternary phospholipid/cholesterol/water systems. However, in contrast to the latter ternary systems, the exchange of lipids between the lo and the ld phases was slow on the timescale for the diffusion experiment for the quarternary ones. This means that on the millisecond timescale fluid, ordered domains are floating around in a sea of faster diffusing lipids, assigned to consist of mainly dioleoylphosphatidylcholine.

  • 14.
    Filippov, Andrey
    et al.
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Orädd, Greger
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Lindblom, Göran
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Sphingomyelin structure influences the lateral diffusion and raft formation in Lipid Bilayers2006Ingår i: Biophysical Journal, ISSN 0006-3495, Vol. 90, nr 6, s. 2086-92Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Liquid-disordered/liquid-ordered two-phase coexistence regions in hydrated bilayers have been investigated for sphingomyelins (SMs) of three different origins: egg, brain, and milk with the pulsed-field gradient NMR technique for lateral diffusion measurement. It is found that the three SMs have the same diffusional behavior in bilayers of SM alone, but in the multicomponent systems of dioleoylphosphatidylcholine/SM/cholesterol, the ability to form domains differs for the three SMs. The two-phase area is more extended for egg SM than for brain SM, and no two-phase coexistence is found for milk SM. The differences in behavior are correlated with the homogeneity of the SM hydrocarbon chain compositions, in which egg SM has the most homogeneous and milk SM has the most heterogeneous composition. The results indicate that a crucial element in the domain-forming process is the formation of highly packed bilayers of SM and cholesterol rather than specific interactions between SM and cholesterol.

  • 15.
    Filippov, Andrey
    et al.
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Orädd, Greger
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Lindblom, Göran
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    The Effect of Cholesterol on the Lateral Diffusion of Phospholipids in Oriented Bilayers2003Ingår i: Biophysical Journal, Vol. 84, s. 3079-86Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Pulsed field gradient NMR was utilized to directly determine the lipid lateral diffusion coefficient for the following macroscopically aligned bilayers: dimyristoylphosphatidylcholine (DMPC), sphingomyelin (SM), palmitoyloleoylphosphatidylcholine (POPC), and dioleoylphosphatidylcholine (DOPC) with addition of cholesterol (CHOL) up to 40 mol %. The observed effect of cholesterol on the lipid lateral diffusion is interpreted in terms of the different diffusion coefficients obtained in the liquid ordered (lo) and the liquid disordered (ld) phases occurring in the phase diagrams. Generally, the lipid lateral diffusion coefficient decreases linearly with increasing CHOL concentration in the ld phase for the PC-systems, while it is almost independent of CHOL for the SM-system. In this region the temperature dependence of the diffusion was always of the Arrhenius type with apparent activation energies (EA) in the range of 28–40 kJ/mol. The lo phase was characterized by smaller diffusion coefficients and weak or no dependence on the CHOL content. The EA for this phase was significantly larger (55–65 kJ/mol) than for the ld phase. The diffusion coefficients in the two-phase regions were compatible with a fast exchange between the ld and lo regions in the bilayer on the timescale of the NMR experiment (100 ms). Thus, strong evidence has been obtained that fluid domains (with size of µm or less) with high molecular ordering are formed within a single lipid bilayer. These domains may play an important role for proteins involved in membrane functioning frequently discussed in the recent literature. The phase diagrams obtained from the analysis of the diffusion data are in qualitative agreement with earlier published ones for the SM/CHOL and DMPC/CHOL systems. For the DOPC/CHOL and the POPC/CHOL systems no two-phase behavior were observed, and the obtained EA:s indicate that these systems are in the ld phase at all CHOL contents for temperatures above 25°C.

  • 16.
    Gorbach, Tetiana
    et al.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Pudas, Sara
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Lundquist, Anders
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Orädd, Greger
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Josefsson, Maria
    Umeå universitet, Samhällsvetenskapliga fakulteten, Enheten för demografi och åldrandeforskning (CEDAR).
    Salami, Alireza
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Aging Research Center, Karolinska Institutet and Stockholm University, Stockholm, Sweden.
    de Luna, Xavier
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Longitudinal association between hippocampus atrophy and episodic-memory decline2017Ingår i: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 51, s. 167-176Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    There is marked variability in both onset and rate of episodic-memory decline in aging. Structural magnetic resonance imaging studies have revealed that the extent of age-related brain changes varies markedly across individuals. Past studies of whether regional atrophy accounts for episodic-memory decline in aging have yielded inconclusive findings. Here we related 15-year changes in episodic memory to 4-year changes in cortical and subcortical gray matter volume and in white-matter connectivity and lesions. In addition, changes in word fluency, fluid IQ (Block Design), and processing speed were estimated and related to structural brain changes. Significant negative change over time was observed for all cognitive and brain measures. A robust brain-cognition change-change association was observed for episodic-memory decline and atrophy in the hippocampus. This association was significant for older (65-80 years) but not middle-aged (55-60 years) participants and not sensitive to the assumption of ignorable attrition. Thus, these longitudinal findings highlight medial-temporal lobe system integrity as particularly crucial for maintaining episodic-memory functioning in older age. 

  • 17. Hohsfield, Lindsay A.
    et al.
    Daschil, Nina
    Orädd, Greger
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Strömberg, Ingrid
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Humpel, Christian
    Vascular pathology of 20-month-old hypercholesterolemia mice in comparison to triple-transgenic and APPSwDI Alzheimer's disease mouse models2014Ingår i: Molecular and cellular neuroscience, ISSN 1044-7431, Vol. 63, s. 83-95Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Several studies have shown that elevated plasma cholesterol levels (i.e. hypercholesterolemia) serve as a risk factor for late-onset Alzheimer's disease (AD). However, it remains unclear how hypercholesterolemia may contribute to the onset and progression of AD pathology. In order to determine the role of hypercholesterolemia at various stages of AD, we evaluated the effects of high cholesterol diet (5% cholesterol) in wild-type (WT; C57BL6) and triple-transgenic AD (3xTg-AD: Psen1, APPSwe, tauB301L) mice at 7, 14, and 20 months. The transgenic APP-Swedish/Dutch/Iowa AD mouse model (APPSwDI) was used as a control since these animals are more pathologically-accelerated and are known to exhibit extensive plaque deposition and cerebral amyloid angiopathy. Here, we describe the effects of high cholesterol diet on: (1) cognitive function and stress, (2) AD-associated pathologies, (3) neuroinflammation, (4) blood-brain barrier disruption and ventricle size, and (5) vascular dysfunction. Our data show that high dietary cholesterol increases weight, slightly impairs cognitive function, promotes glial cell activation and complement-related pathways, enhances the infiltration of blood-derived proteins and alters vascular integrity, however, it does not induce AD-related pathologies. While normal-fed 3xTg-AD mice display a typical AD-like pathology in addition to severe cognitive impairment and neuroinflammation at 20 months of age, vascular alterations are less pronounced. No microbleedings were seen by MRI, however, the ventricle size was enlarged. Triple-transgenic AD mice, on the other hand, fed a high cholesterol diet do not survive past 14 months of age. Our data indicates that cholesterol does not markedly potentiate AD-related pathology, nor does it cause significant impairments in cognition. However, it appears that high cholesterol diet markedly increases stress-related plasma corticosterone levels as well as some vessel pathologies. Together, our findings represent the first demonstration of prolonged high cholesterol diet and the examination of its effects at various stages of cerebrovascular- and AD-related disease.

  • 18. Jeong, Sang Won
    et al.
    O'Brien, David F
    Orädd, Greger
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Lindblom, Göran
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Encapsulation and Diffusion of Water-Soluble Dendrimers in a Bicontinuous Cubic Phase2002Ingår i: Langmuir, Vol. 18, nr 4, s. 1073-6Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Bicontinuous cubic (QII) phases composed of hydrated lipids are a unique mesoporous organic material. The diameter of the water channels in the range of 5-10 nm could be used as a reservoir for macromolecular therapeutic agents. Here, we describe the synthesis of water-soluble poly(amidoamine) (PAMAM) dendrimer derivatives labeled with fluorine and their diffusion in the water channels of a QII phase. A QII phase with Ia3d symmetry was prepared by hydration of a 9:1 molar mixture of polymerizable monoacylglycerol and the corresponding 1,2-diacylglycerol. The dendrimers having fluorine were synthesized by Michael reaction of PAMAM dendrimers with a mixture of ethyl 4,4,4-trifluorocrotonate and methyl acrylate. The hydrated diameter of the fluorinated dendrimer of generation 2.5 (G2.5AFH) is 32.6 Å as measured by 19F NMR. The diffusion coefficient of G2.5AFH at 25 C in the water channels of the QII phase, determined by pulsed field gradient 19F NMR spectroscopy, is 1 × 10-12 m2/s, which is compared to the free diffusion coefficient of the dendrimer in water (1.42 × 10-10 m2/s). These data indicate that small globular proteins or similar molecules can diffuse rapidly enough in stabilized QII phases to be technically useful.

  • 19.
    Karalija, Amar
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Novikova, Liudmila N.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Orädd, Greger
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Wiberg, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Novikov, Lev N.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Differentiation of pre- and postganglionic nerve injury using MRI of the spinal cord2016Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, nr 12, artikel-id e0168807Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Brachial plexus injury (BPI) is a devastating type of nerve injury, potentially causing loss of motor and sensory function. Principally, BPI is either categorized as preganglionic or post- ganglionic, with the early establishment of injury level being crucial for choosing the correct treatment strategy. Despite diagnostic advances, the need for a reliable, non-invasive method for establishing the injury level remains. We studied the usefulness of in vivo mag- netic resonance imaging (MRI) of the spinal cord for determination of injury level. The find- ings were related to neuronal and glial changes. Rats underwent unilateral L4 & L5 ventral roots avulsion or sciatic nerve axotomy. The injuries served as models for pre- and postgan- glionic BPI, respectively. MRI of the L4/L5 spinal cord segments 4 weeks after avulsion showed ventral horn (VH) shrinkage on the injured side compared to the uninjured side. Axotomy induced no change in the VH size on MRI. Following avulsion, histological sections of L4/L5 revealed shrinkage in the VH grey matter area occupied by NeuN-positive neurons, loss of microtubular-associated protein-2 positive dendritic branches (MAP2), pan-neurofila- ment positive axons (PanNF), synaptophysin-positive synapses (SYN) and increase in immunoreactivity for the microglial OX42 and astroglial GFAP markers. Axotomy induced no changes in NeuN-reactivity, modest decrease of MAP2 immunoreactivity, no changes in SYN and PanNF labelling, and a modest increase in OX42 and SYN labeling. Histological and radiological findings were congruent when assessing changes after axotomy, while MRI somewhat underestimated the shrinkage. This study indicates a potential diagnostic value of structural spinal cord MRI following BPI. 

  • 20.
    Karalija, Nina
    et al.
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Wåhlin, Anders
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Ek, Jesper
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Rieckmann, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Papenberg, Goran
    Salami, Alireza
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM). Aging Research Center, Karolinska Institutet & Stockholm University, Tomtebodavägen 18A,S-17165, Stockholm, Sweden.
    Brandmaier, Andreas M.
    Köhncke, Ylva
    Johansson, Jarkko
    Andersson, Micael
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Axelsson, Jan
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Orädd, Greger
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Riklund, Katrine
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Lövdén, Martin
    Lindenberger, Ulman
    Bäckman, Lars
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Cardiovascular factors are related to dopamine integrity and cognition in aging2019Ingår i: Annals of clinical and translational neurology, E-ISSN 2328-9503, Vol. 6, nr 11, s. 2291-2303Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: The aging brain undergoes several changes, including reduced vascular, structural, and dopamine (DA) system integrity. Such brain changes have been associated with age‐related cognitive deficits. However, their relative importance, interrelations, and links to risk factors remain elusive.

    Methods: The present work used magnetic resonance imaging and positron emission tomography with 11C‐raclopride to jointly examine vascular parameters (white‐matter lesions and perfusion), DA D2‐receptor availability, brain structure, and cognitive performance in healthy older adults (n = 181, age: 64–68 years) from the Cognition, Brain, and Aging (COBRA) study.

    Results: Covariance was found among several brain indicators, where top predictors of cognitive performance included caudate and hippocampal integrity (D2DR availability and volumes), and cortical blood flow and regional volumes. White‐matter lesion burden was negatively correlated with caudate DA D2‐receptor availability and white‐matter microstructure. Compared to individuals with smaller lesions, individuals with confluent lesions (exceeding 20 mm in diameter) had reductions in cortical and hippocampal perfusion, striatal and hippocampal D2‐receptor availability, white‐matter microstructure, and reduced performance on tests of episodic memory, sequence learning, and processing speed. Higher cardiovascular risk as assessed by treatment for hypertension, systolic blood pressure, overweight, and smoking was associated with lower frontal cortical perfusion, lower putaminal D2DR availability, smaller grey‐matter volumes, a larger number of white‐matter lesions, and lower episodic memory performance.

    Interpretation: Taken together, these findings suggest that reduced cardiovascular health is associated with poorer status for brain variables that are central to age‐sensitive cognitive functions, with emphasis on DA integrity.

  • 21.
    Lindblom, Göran
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Orädd, Greger
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Lipid lateral diffusion and membrane heterogeneity2009Ingår i: Biochimica et Biophysica Acta - Biomembranes, ISSN 0005-2736, E-ISSN 1879-2642, Vol. 1788, nr 1, s. 234-244Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The pulsed field gradient (pfg)-NMR method for measurements of translational diffusion of molecules in macroscopically aligned lipid bilayers is described. This technique is proposed to have an appreciable potential for investigations in the field of lipid and membrane biology. Transport of molecules in the plane of the bilayer can be successfully studied, as well as lateral phase separation of lipids and their dynamics within the bilayer organizations. Lateral diffusion coefficients depend on lipid packing and acyl chain ordering and investigations of order parameters of perdeuterated acyl chains, using 2H NMR quadrupole splittings, are useful complements. In this review we summarize some of our recent achievements obtained on lipid membranes. In particular, bilayers exhibiting two-phase coexistence of liquid disordered (ld) and liquid ordered (lo) phases are considered in detail. Methods for obtaining good oriented lipid bilayers, necessary for the pfg-NMR method to be efficiently used, are also briefly described. Among our major results, besides determinations of ld and lo phases, belongs the finding that the lateral diffusion is the same for all components, independent of the molecular structure (including cholesterol (CHOL)), if they reside in the same domain or phase in the membrane. Furthermore, quite unexpectedly CHOL seems to partition into the ld and lo phases to roughly the same extent, indicating that CHOL has no strong preference for any of these phases, i. e. CHOL seems to have similar interactions with all of the lipids. We propose that the lateral phase separation in bilayers containing one high Tm and one low Tm lipid together with CHOL is driven by the increasing difficulty of incorporating an unsaturated or prenyl lipid into the highly ordered bilayer formed by a saturated lipid and CHOL, i.e. the phase transition is entropy driven to keep the disorder of the hydrocarbon chains of the unsaturated lipid.

  • 22.
    Lindblom, Göran
    et al.
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Orädd, Greger
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Order and Disorder in a Liquid Crystalline Bilayer: Pulsed Field Gradient NMR Studies of Lateral Phase Separation2007Ingår i: Journal of Dispersion Science and Technology, Vol. 28, s. 55-61Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The pulsed field gradient NMR method utilized for determination of lipid lateral diffusion in macroscopically aligned lipid bilayers is described. This technique is proposed to have an appreciable potential for biophysical investigations in the field of lipid (lipidomics) and membrane biology. Topics like transport of molecules both across and in the plane of the membrane can be studied successfully, as well as the formation of lipid domains and their intrinsic dynamics can be scrutinized. In this review some recent results on lipid membrane systems are presented. In particular investigations, not easily monitored with other spectroscopic methods, of so-called "raft membranes" are presented. In these membranes two-phase coexistence between liquid disordered (ld) and liquid ordered (lo) phases occurs. Methods for obtaining good oriented lipid membranes, necessary for the NMR method to be efficiently used, are also described. Quite unexpectedly, cholesterol (CHOL) seems to partition into both phases to roughly the same extent, indicating that CHOL has no particular preference for any of the ld and lo phases, and that there are no specific interactions between CHOL and saturated lipids. Another interesting observation is that the lateral diffusion is the same for all components, independent of the molecular structure (thus including CHOL), if they reside in the same domain in the membrane.

    Furthermore, it is found that the domain formation process is sensitive to small changes in the phospholipid chain composition and the structure of the sterol. However, more studies are needed to explain the effect on the raft-forming properties from changes in the positions and the number of double bonds in the sterol ring system.

  • 23.
    Lindblom, Göran
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Orädd, Greger
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    What are the driving forces behind domain formation in lipid bilayers?2007Ingår i: Chemistry and Physics of Lipids, 2007Konferensbidrag (Övrigt vetenskapligt)
    Abstract [en]

    Abstracts from the 48th International Conference on the Bioscience of Lipids

  • 24.
    Lindblom, Göran
    et al.
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Orädd, Greger
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Filippov, Andrey
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Lipid lateral diffusion in bilayers with phosphatidylcholine, sphingomyelin and cholesterol: An NMR study of dynamics and lateral phase separation2006Ingår i: Chemistry and Physics of Lipids, Vol. 141, s. 179-84Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Pulsed field gradient (pfg)-NMR measurements of the lipid lateral diffusion coefficients in several macroscopically aligned bilayer systems were summarized from previous and new studies. The aim was to carry out a comparison of the translational dynamics for bilayers with various mixtures of l,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), l,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and chicken egg yolk sphingomyelin (eSM), with or without cholesterol. New useful information was obtained on the dynamics in these lipid bilayers that has not been previously appreciated. Thus, we were able to propose that the driving force behind the phase separation into ld and lo phases evolves from the increasing difficulty to incorpotate DOPC into a highly ordered phase. Our results suggest that DOPC has a preference to be located in a disordered phase, while DPPC and eSM prefer the ordered phase. Quite unexpectedly, CHOL seems to partition into both phases to roughly the same extent, indicating that CHOL has no particular preference for any of the ld or lo phases, and there are no specific interactions between CHOL and saturated lipids.

  • 25.
    Lindblom, Göran
    et al.
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Orädd, Greger
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Rilfors, Leif
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Morein, Sven
    Regulation of Lipid Composition in Acholeplasma laidlawii and Escherichia coli Membranes: NMR Studies of Lipid Lateral Diffusion at Different Growth Temperatures2002Ingår i: Biochemistry, Vol. 41, nr 38, s. 11512-5Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Lipid lateral diffusion coefficients have been directly determined by pulsed field gradient NMR spectroscopy on macroscopically aligned, fully hydrated lamellar phases containing dimyristoylphosphatidylcholine and total lipid extracts from Acholeplasma laidlawii and Escherichia coli. The temperature dependence of the diffusion coefficient was of the Arrhenius type in the temperature interval studied. The sharp increase in the diffusion coefficient at the growth temperature of E. coli obtained by FRAP measurements, using a fluorescent probe molecule (Jin, A. J., Edidin, M., Nossal, R., and Gershfeld, N. L. (1999) Biochemistry 38, 13275-13278), was not observed. Thus, we conclude that the lipid structural properties (i.e., those affecting the lipid phase behavior), rather than the lipid dynamics, are involved in the adjustment of the membrane lipid composition. Further support for this conclusion is given by the finding that lipid extracts from A. laidlawii grown at different temperatures have about the same diffusion coefficients. Finally, the lipid lateral diffusion in bilayers of phospholipids was found to be much faster than that in bilayers of mainly glucolipids, which can be understood in terms of a free volume theory for the diffusion process.

  • 26. Matyszewska, Dorota
    et al.
    Tappura, Kirsi
    Orädd, Greger
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Bilewicz, Renata
    Influence of Perfluorinated Compounds on the Properties of Model Lipid Membranes2007Ingår i: J. Phys. Chem. B, Vol. 111, s. 9908-18Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The influence of selected perfluorinated compounds (PFCs), perfluorooctanoic acid (PFOA) or perfluorooctanesulfonic acid (PFOS), on the structure and organization of lipid membranes was investigated using model membranes-lipid monolayers and bilayers. The simplest model-a lipid monolayer-was studied at the air-water interface using the Langmuir-Blodgett technique with surface pressure and surface potential measurements. Lipid bilayers were characterized by NMR techniques and molecular dynamics simulations. Two phospholipids, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), characterized by different surface properties have been chosen as components of the model membranes. For a DPPC monolayer, a phase transition from the liquid-expanded state to the liquid-condensed state can be observed upon compression at room temperature, while a DMPC monolayer under the same conditions remains in the liquid-expanded state. For each of the two lipids, the presence of both PFOA and PFOS leads to the formation of a more fluidic layer at the air-water interface. Pulsed field gradient NMR measurements of the lateral diffusion coefficient (DL) of DMPC and PFOA in oriented bilayers reveal that, upon addition of PFOA to DMPC bilayers, DL of DMPC decreases for small amounts of PFOA, while larger additions produce an increased DL. The DL values of PFOA were found to be slightly larger than those for DMPC, probably as a consequence of the water solubility of PFOA. Furthermore, 31P and 2H NMR showed that the gel-liquid crystalline phase transition temperature decreased by the addition of PFOA for concentrations of 5 mol % and above, indicating a destabilizing effect of PFOA on the membranes. Deuterium order parameters of deuterated DMPC were found to increase slightly upon increasing the PFOA concentration. The monolayer experiments reveal that PFOS also penetrates slowly into already preformed lipid layers, leading to a change of their properties with time. These experimental observations are in qualitative agreement with the computational results obtained from the molecular dynamics simulations showing a slow migration of PFCs from the surrounding water phase into DPPC and DMPC bilayers.

  • 27.
    Olmedo-Díaz, Sonia
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Estévez-Silva, Héctor
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Institute of Biomedical Technologies (CIBICAN), Tenerife, Spain; Department of Basic Medical Sciences, University of La Laguna, Tenerife, Spain.
    Orädd, Greger
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    af Bjérken, Sara
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Marcellino, Daniel
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Institute of Biomedical Technologies (CIBICAN), Tenerife, Spain.
    Virel, Ana
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    An altered blood–brain barrier contributes to brain iron accumulation and neuroinflammation in the 6-OHDA rat model of Parkinson's disease2017Ingår i: Neuroscience, ISSN 0306-4522, E-ISSN 1873-7544, Vol. 362, s. 141-151Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Brain iron accumulation is a common feature shared by several neurodegenerative disorders including Parkinson's disease. However, what produces this accumulation of iron is still unknown. In this study, the 6-hydroxydopamine (6-OHDA) hemi-parkinsonian rat model was used to investigate abnormal iron accumulation in substantia nigra. We investigated three possible causes of iron accumulation; a compromised blood-brain barrier (BBB), abnormal expression of ferritin, and neuroinflammation. We identified alterations in the BBB subsequent to the injection of 6-OHDA using gadolinium-enhanced magnetic resonance imaging (MRI). Moreover, detection of extravasated IgG suggested that peripheral components are able to enter the brain through a leaky BBB. Presence of iron following dopamine cell degeneration was studied by MRI, which revealed hypointense signals in the substantia nigra. The presence of iron deposits was further validated in histological evaluations. Furthermore, iron inclusions were closely associated with active microglia and with increased levels of L-ferritin indicating a putative role for microglia and L-ferritin in brain iron accumulation and dopamine neurodegeneration.

  • 28.
    Orädd, Greger
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Lipid lateral diffusion in oriented domain-forming model membranes studied by pfg-NMR2007Ingår i: EUCHEM conference 20-22 August 2007, Fiskebäckskil (north of Göteborg), Sweden: Structure Dynamics in Soft Condensed Matter, 2007Konferensbidrag (Övrig (populärvetenskap, debatt, mm))
  • 29.
    Orädd, Greger
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    NMR diffusion studies on lyotropic liquid crystalline systems1994Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    The pulsed field gradient fourier transform nuclear magnetic resonance (PFG-FTNMR) method to measure translational diffusion coefficients in multicomponent systems has been applied to amphiphilic molecules forming liquid crystalline phases.

    By analyzing the concentration dependence of the diffusion coefficients of water and amphiphile in a micellar system of N,N-dimethyldodecy lamine oxide (DDAO) in water it was possible to conclude that the micelles formed were polydisperse in size and shape. It was also shown that solubilization of small amounts of hydrophobic molecules into the micelles induces spherical micelles of a narrow size distribution. From the magnitude of the lateral diffusion coefficient in the cubic phase of DDAO/water it was concluded that this phase is built up of bicontinous aggregates.

    The lipid lateral diffusion in the cubic phase of monooleoylglycerol (MO)/water has been measured. The decrease in the lateral diffusion of MO in this phase, when the water was replaced by glycerol, was ascribed to changes in viscosity in the polar region. Measurements by electron spin resonance and time-resolved fluorescence spectroscopy showed that changes in viscosity of the solvent also affected the motions in the hydrocarbon region.

    The diffusion coefficients of all three components in the cubic phase located in the lowwater region of the ternary system of diacylglycerol (DAG)/soybean phosphatidylcholine (SPC)/water have been determined. Conclusive evidence was provided for that this cubic phase is built up of reversed micelles containing mainly SPC in a continous matrix of mainly DAG.

    The effect on the phase properties of DDAO upon incorporation of the peptide gramicidin D has been investigated. It was shown that gramicidin D induces a lamellar phase at all water contents. The change in the order parameter profile of the C-2H bonds in perdeuterated DDAO upon incorporation of gramicidin D is compatible with theoretical calculations for proteins exhibiting a positive hydrophobic mismatch.

    A method for using the PFG FTNMR technique in measurements of the transmembrane exchange rate of small molecules in vesicular suspensions is discussed and some preliminary data is shown.

  • 30.
    Orädd, Greger
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    NMR Studies of Oriented Domain-Forming Model Membranes2007Ingår i: Bioactive Lipids in the Lipidomics Era (C2), 2007Konferensbidrag (Övrig (populärvetenskap, debatt, mm))
    Abstract [en]

    Summary of Meeting

    The identification of many receptors and targets of bioactive lipid mediators has led to research uncovering their roles in regulating many important normal and pathophysiological processes. It has become evident that the biological activities and functions of lipid signaling molecules are dependent on both their molecular structures and complex cell-specific interactions among the different pathways involved in their biosynthesis and metabolism. The growing complexity of these interactions and the thousands of cellular lipids, together with genomics and proteomics technology already in place, has emphasized the need for development of complementary lipidomics technology. The goal of this meeting is to bring investigators studying signaling and metabolism of bioactive lipids together with researchers who are now developing lipidomics methods for exhaustive characterization and systematic measurement by mass spectrometry of the lipidome, ie cellular lipids, their precursors and their metabolites. The program of this meeting has been designed to foster and synergize research in these areas.

  • 31.
    Orädd, Greger
    et al.
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Edman, Ludvig
    Fysik.
    Ferry, Anders
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Diffusion: a comparision between liquid and solid polymer LiTFSI electrolytes2001Ingår i: 13th International Conference on Solid State Ionics (8-14 July 2001), Cairns, AUSTRALIA, 2001Konferensbidrag (Refereegranskat)
    Abstract [en]

    From careful analyses of pfg-NMR data, it is demonstrated that the size of the diffusing Li+·xH2O complex in an aqueous solution of LiTFSI is strongly dependent on salt concentration, with the number of solvating water units ranging from six in dilute (H2O)500LiTFSI to two in highly concentrated (H2O)5LiTFSI. Such a relationship is explained by a mass tendency toward a lower solvation number as the number of available H2O molecules per lithium ion decreases. In a liquid (PEO)nLiTFSI system, a contrasting situation prevails, since the size of the diffusing Li+ complex is almost constant over a large salt concentration range (5≤n≤50). Our interpretations of these data imply that one PEO chain, containing on average nine ether oxygen units, is able to dissolve up to two lithium ions, but exclude the possibility of cationic crosslinks between different PEO chains and direct ionic interactions. For solid P(EO)nLiTFSI eletrolytes, a significantly lower value for the diffusion coefficient of the small lithium ions as compared to that of the large TFSI ions (DLi=0.2DTFSI) was found for all salt concentrations investigated (5≤n≤50). This observation fits in with recent structural observations, which suggest that lithium ions move as single entities in this specific system and require a rather complicated solvation–desolvation step for long-range motion. In all electrolytes investigated, both liquid and solid, the large and bulky TFSI ion appears to be moving as a single unit, thus manifesting the excellent ionization properties of the LiTFSI salt.

  • 32.
    Orädd, Greger
    et al.
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Edman, Ludvig
    Fysik.
    Ferry, Anders
    Fysik.
    Diffusion: a comparison between liquid and solid polymer LiTFSI electrolytes2002Ingår i: Solid State Ionics, Vol. 152-153, s. 131-6Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    From careful analyses of pfg-NMR data, it is demonstrated that the size of the diffusing Li+·xH2O complex in an aqueous solution of LiTFSI is strongly dependent on salt concentration, with the number of solvating water units ranging from six in dilute (H2O)500LiTFSI to two in highly concentrated (H2O)5LiTFSI. Such a relationship is explained by a mass tendency toward a lower solvation number as the number of available H2O molecules per lithium ion decreases. In a liquid (PEO)nLiTFSI system, a contrasting situation prevails, since the size of the diffusing Li+ complex is almost constant over a large salt concentration range (5≤n≤50). Our interpretations of these data imply that one PEO chain, containing on average nine ether oxygen units, is able to dissolve up to two lithium ions, but exclude the possibility of cationic crosslinks between different PEO chains and direct ionic interactions. For solid P(EO)nLiTFSI eletrolytes, a significantly lower value for the diffusion coefficient of the small lithium ions as compared to that of the large TFSI ions (DLi=0.2DTFSI) was found for all salt concentrations investigated (5≤n≤50). This observation fits in with recent structural observations, which suggest that lithium ions move as single entities in this specific system and require a rather complicated solvation–desolvation step for long-range motion. In all electrolytes investigated, both liquid and solid, the large and bulky TFSI ion appears to be moving as a single unit, thus manifesting the excellent ionization properties of the LiTFSI salt.

  • 33.
    Orädd, Greger
    et al.
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Furlani, M
    Ferry, Anders
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Diffusion and dielectric studies of the system PPO4000–NH4CF3SO31999Ingår i: International Conference(12th) on Solid State Ionics Held in Kassandra, Halkidiki Thessaloniki, Greece on June 6-12, 1999, 1999Konferensbidrag (Refereegranskat)
    Abstract [en]

    A polymer electrolyte system composed of poly(propylene oxide) of molecular weight 4000 (PPO4000) complexed with NH4CF3SO3 (NH4TF) has been investigated by multinuclear pfg-NMR and AC impedance methods. Samples in the concentration range 0.03–0.69 mol/kg (O:NH4 ratios of 500:1–22:1) have been investigated over the temperature range 25–75°C. The combination of AC conductance and pfg-NMR diffusion measurements gives clear evidence that extensive ion-aggregation/clustering occurs at low salt concentrations. With increasing salt-content the Haven ratio, defined as Λcalc/Λexp, decreases from >100 to 2 when going from 0.03 to 0.69 mol/kg. Such gross deviations from the Nernst–Einstein relation (i.e. Λ ∝ D++D−) originate in extensively correlated motions of ions. We interpret the results in terms of labile salt-rich sub-domains being further destabilized through an increase in the dielectric constant of the solution with increasing salt content.

  • 34.
    Orädd, Greger
    et al.
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Furlani, M
    Ferry, Anders
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Diffusion and dielectric studies of the system PPO4000–NH4CF3SO32000Ingår i: Solid State Ionics, Vol. 136-7, s. 457-61Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A polymer electrolyte system composed of poly(propylene oxide) of molecular weight 4000 (PPO4000) complexed with NH4CF3SO3 (NH4TF) has been investigated by multinuclear pfg-NMR and AC impedance methods. Samples in the concentration range 0.03–0.69 mol/kg (O:NH4 ratios of 500:1–22:1) have been investigated over the temperature range 25–75°C. The combination of AC conductance and pfg-NMR diffusion measurements gives clear evidence that extensive ion-aggregation/clustering occurs at low salt concentrations. With increasing salt-content the Haven ratio, defined as Λcalc/Λexp, decreases from >100 to 2 when going from 0.03 to 0.69 mol/kg. Such gross deviations from the Nernst–Einstein relation (i.e. Λ ∝ D++D−) originate in extensively correlated motions of ions. We interpret the results in terms of labile salt-rich sub-domains being further destabilized through an increase in the dielectric constant of the solution with increasing salt content.

  • 35.
    Orädd, Greger
    et al.
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Gustafsson, Jonas
    Almgren, Mats
    Intermediate phases in the system egg lecithin/CTAC/brine. SAXS and NMR studies2001Ingår i: Langmuir, ISSN 0743-7463, Vol. 17, nr 11, s. 3227-34Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The phase behavior and phase structures in the pseudo ternary system egg lecithin (EPC)/ cetyltrimethylammonium chloride/brine (100 mM NaCl) have been investigated by H-2 and P-31 NMR spectroscopy and small-angle X-ray diffraction (SAXS). At solvent contents higher than 55 wt %, micellar, hexagonal, and lamellar phases are formed. At lower solvent content, an intermediate phase occurs consisting of rods with noncircular cross-sections farming a centered rectangular phase of space symmetry c2mm. This phase is connected to both the lamellar phase and the hexagonal phase by two-phase regions. There is a large region of the lamellar phase where the bilayers contain water-filled defects in the form of pores and/or slits. SAXS diffractograms from the defect lamellar phase exhibit interlamellar Bragg reflections as well as a broad reflection originating from the water-filled defects. The variation of the distances obtained as a function of water content and CTAC/EPC ratio is consistent with theoretical predictions on water-filled defects in lamellae. The rectangular phase is characterized by several sharp SAXS reflections which have been indexed to the space group c2mm. The NMR line shapes are of biaxial symmetry with an asymmetry parameter ranging from 0.6 to 1.0. From an analysis of the SAXS and NMR data, we have found evidence of molecular segregation in that lecithin is enriched in the flat regions of the noncircular cylinders.

  • 36.
    Orädd, Greger
    et al.
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Lindblom, Göran
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Lateral diffusion coefficients of raft lipids from pulsed field gradient NMR2007Ingår i: Methods in Molecular Biology: Lipid Rafts, Humana Press Inc, Totowa, NJ , 2007Kapitel i bok, del av antologi (Refereegranskat)
    Abstract [en]

    The pulsed field gradient-nuclear magnetic resonance diffusion technique has an appreciable potential for biophysical investigations in membrane biology, various lyotropic liquid crystals, and other complex fluid systems. In particular, topics like transport of molecules both across and within the plane of a lipid membrane can be successfully studied, as well as the formation of lipid domains and their intrinsic dynamics. The pulsed field gradient-nuclear magnetic resonance technique and the preparation of oriented samples for investigations of lipid lateral diffusion in macroscopically aligned bilayers, oriented by a goniometer probe in the main magnetic field, are described. Some recent results illustrating the potential of the method in detecting and characterizing domain formation are also presented.

    Keywords: Lateral diffusion, PFG-NMR, phospholipids, cholesterol, lateral phase separation, domains, liquid-ordered phase, liquid-disordered phase

  • 37.
    Orädd, Greger
    et al.
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Lindblom, Göran
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Lateral diffusion studied by pulsed field gradient NMR on oriented lipid membranes2004Ingår i: Magnetic Resonance in Chemistry, Vol. 42, nr 2, s. 123-31Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    This mini-review focuses on the utilization of pulsed magnetic field gradients to measure diffusional motion in systems of macroscopically oriented lipid bilayers. The NMR diffusion technique is proposed to have appreciable potential for future biophysical investigations in the field of membrane biology. Topics such as transport of molecules both across and in the plane of the membrane can be successfully studied, and the formation of lipid domains and their intrinsic dynamics can also be scrutinized. First, a short introduction to the NMR technique is given together with a brief discussion on methods of obtaining a good bilayer orientation. Then, a number of recent results on biophysical/biological membrane systems of great interest is presented, in which some unique conclusions on so-called raft membranes are reached. It is shown for systems with large two-phase areas of liquid disordered and liquid ordered phases that lipid lateral diffusion is faster in the former phase and has a smaller apparent activation energy. Further, on the time-scale of the experiments (50-250 ms), exchange between the two phases is fast in the phospholipid-cholesterol-water ternary system, whereas it is slow in the sphingomyelin-dioleoylphosphatidylcholine-cholesterol-water quaternary system.

  • 38.
    Orädd, Greger
    et al.
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Lindblom, Göran
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    NMR in macroscopically oriented lyotropic systems2003Ingår i: In NMR of ordered liquids, Kluwer Academic Publishers, Dordrecht , 2003, s. 399-418Kapitel i bok, del av antologi (Refereegranskat)
  • 39.
    Orädd, Greger
    et al.
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Lindblom, Göran
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    NMR Studies of Lipid Lateral Diffusion in the DMPC/Gramicidin D/Water System: Peptide Aggregation and Obstruction Effects2004Ingår i: Biophysical Journal, Vol. 87, s. 980-7Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The PFG-NMR method has been used in macroscopically oriented bilayers to investigate the effect of the peptide gramicidin D on the lateral diffusion of dimyristoylphosphatidylcholine. By varying both the temperature (21–35°C) and the gramicidin content (0–5 mol %) we have introduced solid obstacles into the lipid liquid crystalline bilayer. It was shown that the obstruction effect exerted by the peptide can be described with several different theoretical models, each based on different premises, and that the fit of the models to experimental data gave reasonable results. We found that each gramicidin molecule was surrounded by approximately one layer of bound lipids and that the obstruction from gel phase patches can be described as small solid obstacles. No evidence of linear aggregates of gramicidin, such as those reported by atomic force microscopy in the gel phase, was found.

  • 40.
    Orädd, Greger
    et al.
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Lindblom, Göran
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Pfg NMR studies of lateral diffusion in oriented lipid bilayers2005Ingår i: SPECTROSCOPY-AN INTERNATIONAL JOURNAL, ISSN 0712-4813, Vol. 19, nr 4, s. 191-8Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The pfg-NMR diffusion technique is proposed to have an appreciable potential for future biophysical investigations in the field of membrane biology. Topics like transport of molecules both across and in the plane of the membrane can be successfully studied, as well as the formation of lipid domains and their intrinsic dynamics can be scrutinized. This short review will introduce the fundamental aspects of orientation dependent NMR interactions and the technique of macroscopically oriented bilayers for eliminating the unwanted effects of those interactions. The pfg-NMR technique will be briefly introduced and finally, some recent results illustrating the potential of the method are presented.

  • 41.
    Orädd, Greger
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Lindblom, Göran
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Halling, K
    Nyholm, T K M
    NMR studies of binary and ternary systems of phosphatidylcholines2007Ingår i: European Biophysics Journal, 2007 July, Volume 36, Supplement 1: 6th EBSA & British Biophysical Society Congress July 14-18 2007, Imperial College, London, U.K. - Abstracts, 2007, s. 1-278Konferensbidrag (Övrigt vetenskapligt)
    Abstract [en]

    Lipid lateral segregation in biomimicking model membranes has recently become a topic of great interest due to the biological coupling to the concept of functional rafts. In the studies of liquid-liquid phase coexistence it is found that lateral phase separation into liquid ordered and liquid disordered phases takes place in ternary systems consisting of one unsaturated and one saturated lipid, together with a sterol. The phase behavior is critically dependent on the components with respect to chain length, degree of unsaturation and sterol structure and the driving force of the phase separation is closely related to the ordering effect of the sterol on the lipid chains. This study presents NMR data for binary and ternary systems composed

    of mixtures of sphingomyelins, phosphatidylcholines and cholesterol. Order parameters were obtained from perdeuterated

    chains in the saturated lipid and diffusion data of both the saturated and unsaturated lipids were measured with the pulsed field gradient NMR method. Data were analyzed with regard to phase separation into liquid and solid phases.

  • 42.
    Orädd, Greger
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Lindblom, Göran
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Halling, Katrin K
    Nyholm, Thomas K M
    Slotte, J Peter
    Lipid lateral diffusion in binary and ternary systems of phosphatidylcholines, sphingomyelins and sterols studied by pfg-NMR2007Ingår i: Chemistry and Physics of Lipids, 2007, s. S13-S14Konferensbidrag (Övrigt vetenskapligt)
    Abstract [en]

    Abstracts from the 48th International Conference on the Bioscience of Lipids

  • 43.
    Orädd, Greger
    et al.
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Lindblom, Göran
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Westerman, Philip W
    Lateral Diffusion of Cholesterol and Dimyristoylphosphatidylcholine in a Lipid Bilayer Measured by Pulsed Field Gradient NMR Spectroscopy2002Ingår i: Biophys Journal, Vol. 83, nr 5, s. 2702-4Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The pulsed field gradient NMR method for measuring self-diffusion has been used for a direct determination of the lateral diffusion coefficient of cholesterol, fluorine labeled at the 6-position, for an oriented lamellar liquid-crystalline phase of dimyristoylphosphatidylcholine (DMPC)/cholesterol/water. It is found that the diffusion coefficients of DMPC and cholesterol are equal over a large temperature interval. The apparent energy of activation for the diffusion process (58 kJ/mol) is about the same as for a lamellar phase of DMPC/water, whereas the phospholipid lateral diffusion coefficient is approximately four times smaller in the presence of cholesterol.

  • 44.
    Orädd, Greger
    et al.
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Rilfors, Leif
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Lindblom, Göran
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Initial acyl chain segments of gluco- and phospholipids differ in ordering in both lamellar and reversed hexagonal phases2001Ingår i: Phys Chem Chem Phys, Vol. 3, s. 5052-8Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    2H-NMR studies of three synthetic phospholipids and two glucolipids from Acholeplasma laidlawii, all having C2-deuterated acyl chains, have been performed. In the lamellar liquid crystalline (L) phase the phospholipids generate three Pake doublets with large differences in magnitude, while only two Pake doublets of similar magnitude are recorded from the glucolipids because of overlap between the two outer splittings. In an L phase with one phospholipid and one glucolipid a superposition of the individual 2H-NMR spectra is obtained. These results point to a distinct difference in the conformations of the initial segments of the acyl chains in the two lipid classes, and to the fact that the two acyl chains in the glucolipids have more similar average conformations of the initial segments. Furthermore, the results imply that the two lipids retain their respective acyl chain and glycerol backbone conformations in the mixtures. We report, for the first time, that separate quadrupole splittings are obtained from the sn-1 and each of the sn-2 deuterons present in phospholipids forming a reversed hexagonal (HII) phase. In contrast, glucolipids generate just one splitting in an HII phase. These results indicate that both the phospholipids and the glucolipids essentially retain their respective conformations of the acyl chains and the glycerol backbone upon a transition from an L to an HII phase. It is speculated that the different appearance of the spectra obtained from the glucolipids is achieved by slightly tilting the glycerol backbone relative to the normal of the bilayer surface. The reason for the tilting may be that the non-ionic, less hydrophilic, glucolipid headgroups are somewhat more deeply positioned in the interfacial polarity gradient of the bilayer than the ionic phosphate-containing headgroups.

  • 45.
    Orädd, Greger
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Schmidtchen, Artur
    Malmsten, Martin
    Effects of peptide hydrophobicity on its incorporation in phospholipid membranes - an NMR and ellipsometry study2011Ingår i: Biochimica et Biophysica Acta, ISSN 0006-3002, E-ISSN 1878-2434, Vol. 1808, nr 1, s. 244-252Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Effects of peptide hydrophobicity on lipid membrane binding, incorporation, and defect formation was investigated for variants of the complement-derived antimicrobial peptide CNY21 (CNYITELRRQHARASHLGLAR), in anionic 1-palmitoyl-2-oleoylphosphatidylethanolamine (POPE)/1-palmitoyl-2-oleoylphosphatidylglycerol (POPG) and zwitterionic 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) membranes. Using a method combination of, e.g., ellipsometry, CD, and fluorescence spectroscopy, it was shown that peptide adsorption, as well as peptide-induced liposome leakage and bactericidal potency against Escherichia coli and Pseudomonas aeruginosa, was promoted by increasing the hydrophobicity of CNY21 through either substituting the two histidines (H) in CNY21 with more hydrophobic leucine (L) residues, or end-tagging with tritryptophan (WWW). Fluorescence spectroscopy revealed that both CNY21WWW and the WWW tripeptide localized to the polar headgroup region of these phospholipid membranes. Deuterium NMR experiments on macroscopically oriented membranes containing fully (palmitoyl) deuterated POPC (POPC-d(31)) demonstrated that both CNY21L and CNY21WWW induced disordering of the lipid membrane. In contrast, for cholesterol-supplemented POPC-d(31) bilayers, peptide-induced disordering was less pronounced in the case of CNY21L, indicating that the peptide is unable to partition to the interior of the lipid membrane in the presence of cholesterol. CNY21WWW, on the other hand, retained its membrane-disordering effect also for cholesterol-supplemented POPC-d(31). These findings were supported by pulsed field gradient NMR experiments where the lateral lipid diffusion was determined in the absence and presence of peptides. Overall, the results provide some mechanistic understanding to previously observed effects of peptide hydrophobization through point mutations and end-tagging, particularly so for complement-based antimicrobial peptides.

  • 46.
    Orädd, Greger
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Shahedi, Vahid
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Lindblom, Göran
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Effect of sterol structure on the bending rigidity of lipid membranes: A 2H NMR transverse relaxation study2009Ingår i: Biochimica et Biophysica Acta - Biomembranes, ISSN 0005-2736, E-ISSN 1879-2642, Vol. 1788, nr 9, s. 1762-1771Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The effect of incorporation of 3–43 mol% sterol on the lipid order and bilayer rigidity has been investigated for model membranes of dimyristoylphosphatidylcholine or dipalmitoylphosphatidylcholine. 2H NMR spectra and spin-lattice relaxation rates were measured for macroscopically aligned bilayers. The characteristics of spectra obtained at temperatures between 0–60 °C are interpreted in terms of a two-phase coexistence of the liquid disordered and the liquid ordered phases and the data is found to be in agreement with the phase diagram published by Vist and Davis (Biochemistry 29 (1990), pp. 451–464). The bending modulus of the bilayers was calculated from plots of relaxation rate vs. the square of the order parameter at 44 °C. Clear differences were obtained in the efficiency of the sterols to increase the stiffness of the bilayers. These differences are correlated to the ability of the sterols to induce the liquid ordered phase in binary as well as in ternary systems; the only exception being ergosterol, which was found to be unable to induce lo phases and also had a relatively weak effect on the bilayer stiffness in contrast to earlier reports.

  • 47.
    Orädd, Greger
    et al.
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Westerman, PW
    Lindblom, Göran
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Lateral diffusion coefficients of separate lipid species in a ternary raft-forming bilayer: A Pfg-NMR multinuclear study2005Ingår i: BIOPHYSICAL JOURNAL, ISSN 0006-3495, Vol. 89, nr 1, s. 315-20Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    By isotopical labeling lipid lateral diffusion coefficients for each of the membrane constituents, including cholesterol, have been measured by H-1, H-2, and F-19 pulsed field gradient NMR spectroscopy in macroscopically oriented lipid bilayers. This provides a means of obtaining detailed dynamic and compositional information in raft-forming lipid bilayers without introducing foreign molecules into the systems. The raft systems studied contained dioleoylphosphatidylcholine/dipalmitoylphosphatidylcholine (DPPC)/cholesterol at the molar ratios of 42.5: 42.5: 15 and 35: 35: 30 in excess water. At temperatures below 30 degrees C the raft system forms large (>1 mu m) domains of a liquid ordered (l(o)) phase, in which the lipid lateral diffusion was; 5 times slower than for the lipids in the surrounding liquid disordered (l(d)) phase. Within each domain all lipid species showed the same diffusion coefficient, despite the very different structures of cholesterol and phospholipids. DPPC partitions exclusively into the l(o) domains, whereas cholesterol and dioleoylphosphatidylcholine were distributed in both l(o) and l(d) phases. The cholesterol concentration was found to be 10-20 mol% in the l(d) domain and 30-40 mol% in the l(o) domain. Comparison of these results with data from sphingomyelin-containing systems suggests that DPPC interacts more weakly with cholesterol than does sphingomyelin.

  • 48.
    Shahedi, Vahid
    et al.
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Orädd, Greger
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Lindblom, Göran
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Domain-formation in DOPC/SM bilayers studied by pfg-NMR: Effect of sterol structure2006Ingår i: Biophys Journal, ISSN 0006-3495, Vol. 91, nr 7, s. 2501-7Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Pulsed field gradient (pfg)-NMR spectroscopy was utilized to determine lipid lateral diffusion coefficients in oriented bilayers composed of 25 mol % sterol and equimolar amounts of dioleoylphosphatidylcholine and sphingomyelin. The occurrence of two lipid diffusion coefficients in a bilayer was used as evidence of lateral phase separation into liquid ordered and liquid disordered domains. It was found that cholesterol, ergosterol, sitosterol, and lathosterol induced domains, whereas lanosterol, stigmasterol, and stigmastanol resided in homogeneous membranes in the temperature interval of 24-70 degrees C. Among the domain-forming sterols, differences in the upper miscibility temperature indicated that the stability of the liquid ordered phase could be modified by small changes in the sterol structure. The domain-forming capacity for the different sterols is discussed in terms of the ordering effect of the sterols on the lipids, and it is proposed that the driving force for the lateral phase separation is the reduced solubility of the unsaturated lipid in the highly ordered phase.

  • 49.
    Strömberg, Ingrid
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Histologi med cellbiologi.
    Rehnmark, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Histologi med cellbiologi.
    Orädd, Greger
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Histologi med cellbiologi.
    Virel, Ana
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Histologi med cellbiologi.
    Neuroinflammation Using MRI: Phagocytes From Blood to Brain With the Help of Bilberries2013Ingår i: Cell Transplantation, ISSN 0963-6897, E-ISSN 1555-3892, Vol. 22, nr 5, s. 917-917Artikel i tidskrift (Övrigt vetenskapligt)
  • 50.
    Vaziri, Mojgan
    et al.
    Department of Wood Science and Technology, Luleå University of Technology.
    Orädd, Greger
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Lindgren, Owe
    Department of Wood Science and Technology, Luleå University of Technology,.
    Pizzi, Antonio
    Magnetic resonance imaging of water distribution in welded woods2011Ingår i: Journal of Adhesion Science and Technology, ISSN 0169-4243, E-ISSN 1568-5616, Vol. 25, nr 16, s. 1997-2003Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    This study was performed for a better understanding of water effect on welded wood and improving its water resistance. In this article, we have also attempted to demonstrate the feasibility of using Magnetic Resonance Imaging technology to study water movement in welded woods. Water distribution in welded woods of Scots pine (Pinus sylvestris) and beech (Fagus sylvatica) was investigated by Magnetic Resonance Imaging. Axial specimens were cut from beech and sapwood of Scots pine in longitudinal direction of wood grain. Two pieces of each wood species were welded together by a linear vibration machine. Sub-samples measuring 30 mm x 20 mm x 100 mm were cut from the welded specimens for Magnetic Resonance Imaging. The results showed that weldline of Scots pine was more resistant to water than weldline of beech. Pine joint was still holding after 40 h immersion in water, while a rapid wetting of the beech joint resulted in breakage of the joint in even less than an hour. This preliminary study also showed that MRI is a powerful tool to measure water distribution in welded woods and highlighted the potential of this technique to enhance understanding of wood welding. (C) Koninklijke Brill NV, Leiden, 2011

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