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  • Impact of the ceramide subspecies on the nanostructure of stratum corneum lipids using neutron scattering and molecular dynamics simulations. Part I: Impact of CER[NS]
    Chem. Phys. Lipids (IF 3.361) Pub Date : 2018-05-30
    Thomas Schmitt, Rakesh Gupta, Stefan Lange, Stefan Sonnenberger, Bodo Dobner, Thomas Hauß, Beena Rai, Reinhard H.H. Neubert
  • On the Prediction of Critical Micelle Concentration for Sugar-Based Non-Ionic Surfactants
    Chem. Phys. Lipids (IF 3.361) Pub Date : 2018-05-30
    Alireza Baghban, Jafar Sasanipour, Mohsen Sarafbidabad, Amin Piri, Razieh Razavi

    Micellization phenomenon occurs in natural and technical processes, necessitating the need to develop predictive models capable of predicting self-assembly behavior of surfactants. A least squares support vector machine (LSSVM) based quantitative structure property relationships (QSPR) model is developed in order to predict critical micelle concentration (CMC) for sugar-based surfactants. Model development is based on training and validating a predictive LSSVM strategy using a comprehensive data base consisting of 83 sugar-based surfactants. Model’s reliability and robustness has been evaluated using different visual and statistical parameters, revealing its great predictive capabilities. Results are also compared to previously reported best multi-linear regression (BMLR) based QSPR and group contribution based models, showing better performance of the proposed LSSVM-based QSPR model regarding lower RMSE value of 0.023 compared to the group contribution based and the best results from BMLR-based QSPR.

    Chem. Phys. Lipids (IF 3.361) Pub Date : 2018-05-29
    G.K. Vladimirov, A.S. Vikulina, D.V. Volodkin, Yu.A. Vladimirov
  • Regulation of Endogenic Metabolites by Rosuvastatin in Hyperlipidemia Patients: An Integration of Metabolomics and Lipidomics
    Chem. Phys. Lipids (IF 3.361) Pub Date : 2018-05-28
    Hyunbeom Lee, Jong Min Choi, Joo-Youn Cho, Tae-Eun Kim, Hwa Jeong Lee, Byung Hwa Jung

    Rosuvastatin is a statin used to treat metabolic syndrome conditions, such as hyperlipidemia. It is relatively safe; however, fatal rhabdomyolysis or skeletal myopathy can sometimes occur. Therefore, to investigate the overall effects of rosuvastatin, including lipid lowering and adverse effects, metabolic profiling was performed using metabolomics and lipidomics after rosuvastatin administration. Specifically, the metabolic profiles between healthy subjects and patients with hyperlipidemia were compared and the metabolic changes related to the mechanism of the drug effect were proposed. Healthy volunteers (n = 32) and hyperlipidemic patients (n = 14) were orally administered rosuvastatin (20 mg) once a day for 3-8 weeks, and plasma and urine were collected. Metabolomics and lipidomics were performed using UHPLC-LTQ/Orbitrap/MS/MS for non-targeted analysis and UHPLC-TQ-MS/MS for targeted analysis. Using non-targeted analysis, we successfully profiled and identified 73 and 87 metabolites in healthy subjects and hyperlipidemia subjects, respectively. Through targeted analysis, we have also quantified 188 metabolites, including amino acids, biogenic amines, glycerophospholipids, and sphingolipids. The levels of L-carnitine, diacylglycerol, and acylcarnitines significantly decreased after rosuvastatin administration regardless of the group. The overall levels of fatty acids (FA) and lysophosphatidylcholines (LysoPC) increased, while phosphatidylcholines (PC) decreased only in the patient group. β-Oxidation decreased overall, while the production of polyunsaturated FA increased only in the hyperlipidemic patients. Using metabolic profiling, we have evaluated the alterations in the biochemical pathways, which may aid in a more detailed understanding of the effect of rosuvastatin. Patient-specific metabolomic and lipidomic profiles may serve as valuable markers for the understanding of the adverse effects associated with statin treatment.

  • 更新日期:2018-05-27
  • Topical treatments with acylceramide dispersions restored stratum corneum lipid lamellar structures in a reconstructed human epidermis model
    Chem. Phys. Lipids (IF 3.361) Pub Date : 2018-05-23
    Akina Nakaune-Iijima, Akinori Sugishima, Gen Omura, Hiroyuki Kitaoka, Tomoko Tashiro, Shigeki Kageyama, Ichiro Hatta

    Long-periodicity phase (LPP) lamellar structures in intercellular lipid matrixes of the stratum corneum (SC) are considered important for maintenance of skin permeability barriers. Acylceramides are essential components of LPP structures, and their absence influences skin barriers under physiological and pathological conditions, such as atopic dermatitis and dry skin. Although topical applications of acylceramide have been shown to facilitate maintenance of the skin barrier, it is unknown whether topically applied acylceramides are incorporated into intercellular lipids to form LPP structures. Thus, we assessed the effects of topical treatments with monomodal acylceramides on the formation of LPP structures in a surfactant-insulted reconstructed human epidermis model using small-angle X-ray scattering (SAXS) and transmission electron microscopy (TEM) analyses. In SAXS experiments, LPP structures give rise to a diffraction peak which indicates the presence of a structure with a 13 nm real space repeat distance. LPP patterns of intercellular lipid matrixes in the SC were disrupted’ by surfactant treatments and were recovered by topical acylceramide treatments. TEM images also showed specific repeating patterns of LPP structures, indicating that topical acylceramide treatments facilitate recovery of LPP structures in the SC. The present data show that the application of acylceramides might temporarily modify the lipid structure to resemble that of normal skin although the underlying cause of dry or diseased skin is not fully clarified.

  • Sphingomyelin Ability to Act as Chiral Selector using Nanodisc Electrokinetic Chromatography
    Chem. Phys. Lipids (IF 3.361) Pub Date : 2018-05-10
    William M. Penny, Christopher P. Palmer

    Understanding how stereochemistry affects interactions with cell membranes is important for effective drug development. Chirality has been shown to greatly effect pharmaceutical distribution and metabolism within the cell. However it has been thought that interactions with, and passive diffusion through, the membrane are not stereochemically selective. Various studies have produced conflicting results regarding whether interactions with lipid bilayers are or can be stereoselective. In the current work, stereoselective interactions between a pair of atropisomers, R-(+)/(S)-(−) 1,1′-Bi-2-naphthol, and sphingomyelin nanodisc bilayers, are demonstrated. This is accomplished using nanodisc electrokinetic chromatography, demonstrating that this approach is sensitive to subtle differences in affinity between small molecule probes and lipid bilayers. Using the same approach, no evidence of stereoselectivity was observed using enantiomer or diastereomer probes of varied chemistry and structure.

  • How Cardiolipin Peroxidation Alters the Properties of the Inner Mitochondrial Membrane?
    Chem. Phys. Lipids (IF 3.361) Pub Date : 2018-05-01
    Marjut Vähäheikkilä, Tapio Peltomaa, Tomasz Róg, Mario Vazdar, Sanja Pöyry, Ilpo Vattulainen

    Cardiolipins have multiple vital functions within biological cell membranes, most notably in the energy metabolism associated with the inner mitochondrial membrane. Considering their essential role, peroxidation of cardiolipins may plausibly have significant effects, as peroxidation is known to alter the functionality of lipid molecules. We used atomistic molecular dynamics simulations to study how peroxidation of cardiolipin affects the properties of the inner mitochondrial membrane. To this end, we explored what happens when varying fractions of fatty acid chains of cardiolipin are replaced by its four different oxidized products in systems modeling the inner mitochondrial membrane. We found that the oxidation of cardiolipin leads to a conformational change both in the backbone/head group and in chain regions of oxidized cardiolipin molecules. The oxidized groups were observed to shift closer to the membrane-water interface region, where they formed hydrogen bonds with several other groups. Additionally, the conformational change turned out to decrease bilayer thickness, and to increase the area per lipid chain, though these changes were minor. The acyl chain conformational order of unoxidized lipids exposed to interactions with oxidized cardiolipins was increased in carbons 3–5 and decreased in carbons 13–17 due to the structural reorganization of the cardiolipin molecules. Overall, the results bring up that the conformation of cardiolipin is altered upon oxidation, suggesting that its oxidation may interfere its interactions with mitochondrial proteins and thereby affect cardiolipin-dependent cellular processes such as electron and proton transport.

  • Highly Effective Solvent Free Esterification of Phytosterols Employing Edible Metal Oxide-Emulsifier as Catalyst
    Chem. Phys. Lipids (IF 3.361) Pub Date : 2018-05-01
    Huina Ruan, Lujing Xu, Shan Hong, Songbai Liu

    A general highly efficient solvent-free esterification of phytosterols with edible magnesium oxide and Span-60 emulsifier catalyst system has been developed. The edible emulsifier dramatically promotes the catalyzing activity of the metal oxide in the reaction. The loading of the magnesium oxide is as low as 0.1 wt% to phytosterols and far lower than the known ones. As demonstrated by the results of scanning electro-microscopy (SEM), the synergistic effect of emulsifier and magnesium oxide presumably results from elimination of nano-scale interfacial barrier between phytosterols and fatty acids and facilitation of mass transfer of reaction agents. The mild, environmentally benign, and highly effective nature of this catalytic transformation suggests its great potential applications.

  • Phase behavior of palmitoyl and egg sphingomyelin
    Chem. Phys. Lipids (IF 3.361) Pub Date : 2018-04-22
    Zoran Arsov, Emilio J. González-Ramírez, Felix M. Goñi, Stephanie Tristram-Nagle, John F. Nagle

    Despite the biological significance of sphingomyelins (SMs), there is far less structural information available for SMs compared to glycerophospholipids. Considerable confusion exists in the literature regarding even the phase behavior of SM bilayers. This work studies both palmitoyl (PSM) and egg sphingomyelin (ESM) in the temperature regime from 3 °C to 55 °C using X-ray diffraction and X-ray diffuse scattering on hydrated, oriented thick bilayer stacks. We observe clear evidence for a ripple phase for ESM in a large temperature range from 3 °C to the main phase transition temperature (TM) of ∼38 °C. This unusual stability of the ripple phase was not observed for PSM, which was in a gel phase at 3 °C, with a gel-to-ripple transition at ∼24 °C and a ripple-to-fluid transition at ∼41 °C. We also report structural results for all phases. In the gel phase at 3 °C, PSM has chains tilted by ∼30° with an area/lipid ∼45 Å2 as determined by wide angle X-ray scattering. The ripple phases for both PSM and ESM have temperature dependent ripple wavelengths that are ∼145 Å near 30 °C. In the fluid phase, our electron density profiles combined with volume measurements allow calculation of area/lipid to be ∼64 Å2 for both PSM and ESM, which is larger than that from most of the previous molecular dynamics simulations and experimental studies. Our study demonstrates that oriented lipid films are particularly well-suited to characterize ripple phases since the scattering pattern is much better resolved than in unoriented samples.

  • Assessing Topology and Surface Orientation of an Antimicrobial Peptide Magainin 2 using Mechanically Aligned Bilayers and Electron Paramagnetic Resonance Spectroscopy
    Chem. Phys. Lipids (IF 3.361) Pub Date : 2018-04-22
    Daniel J. Mayo, Indra D. Sahu, Gary A. Lorigan

    Aligned CW-EPR membrane protein samples provide additional topology interactions that are absent from conventional randomly dispersed samples. These samples are aptly suited to studying antimicrobial peptides because of their dynamic peripheral topology. In this study, four consecutive substitutions of the model antimicrobial peptide magainin 2 were synthesized and labeled with the rigid TOAC spin label. The results revealed the helical tilts to be 66° ± 5°, 76° ± 5°, 70° ± 5°, and 72° ± 5° for the TOAC substitutions H7, S8, A9, and K10 respectively. These results are consistent with previously published literature. Using the EPR (electron paramagnetic resonance) mechanical alignment technique, these substitutions were used to critically assess the topology and surface orientation of the peptide with respect to the membrane. This methodology offers a rapid and simple approach to investigate the structural topology of antimicrobial peptides.

  • Molecular Dynamics Simulations of Glyphosate in a DPPC Lipid Bilayer ☆
    Chem. Phys. Lipids (IF 3.361) Pub Date : 2018-04-21
    Ezequiel N. Frigini, J.J. López Cascales, Rodolfo D. Porasso

    Extensive Molecular Dynamics simulations have been performed to study the effect of Glyphosate (in their neutral and charged forms, GLYP and GLYP2−, respectively) on fully hydrated DiPalmitoylPhosphatidylCholine (DPPC) lipid bilayer. First, we calculated the free energy profile (using the Umbrella Sampling technique) for both states of charge of glyphosate. The minimum value for the free energy for GLYP is ∼−60 kJ.mol−1 located at z =±1.7 nm (from the lipid bilayer center), and there is almost no maximum at the center of the lipid bilayer. By contrast, the minimum for GLYP2− is ∼−35 kJ.mol−1 located at z =± 1.4 nm (from the lipid bilayer center), and the maximum reaches ∼35 kJ.mol−1 at the center of the lipid bilayer. Then, different lipid bilayer properties were analyzed for different Glyphosate:Lipid (G:L) ratios. The mean area per lipid was slightly affected, increasing only 5% (in the presence of glyphosate at high concentrations), which is in agreement with the slight decrease in deuterium order parameters. As for the thickness of the bilayer, it is observed that the state of charge produces opposite effects. On one hand, the neutral state produces an increase in the thickness of the lipid bilayer; on the other, the charged form produces a decrease in the thickness, which not depend linearly on the G:L ratios, either. The orientation of the DPPC head groups is practically unaffected throughout the range of the G:L ratios studied. Finally, the mobility of the lipids of the bilayer is strongly affected by the presence of glyphosate, considerably increasing its lateral diffusion coefficient noteworthy (one order of magnitude), with increasing G:L ratio.

  • Morphology, compressibility and viscoelasticity of the mixed lipid monolayers in the presence of β-carotene
    Chem. Phys. Lipids (IF 3.361) Pub Date : 2018-04-05
    Katarzyna Dopierała, Marta Skrzypiec

    The aim of the present study was to investigate the interfacial behaviour of model biomembranes in the presence of β-carotene (βC). The Langmuir monolayer technique was used to form the mixed lipid film at the air/water interface. Using the surface pressure-area isotherms, the surface potential-area curves and the Brewster angle microscopy the nature of interactions between carotenoid and lipid components of the monolayers was investigated. The results were obtained for complex models of the lipid bilayer composed of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and cholesterol (CHOL). It was found that β-carotene affected the membrane stability, fluidity and rigidity, however this influence varied with the DPPC/CHOL ratio. The membrane permeability which is significant for biological functions was found to be affected by the presence of β-carotene in the membrane. The morphology of mixed films visualized by Brewster angle microscopy was similar for DPPC/CHOL and DPPC/CHOL/βC films indicating incorporation of carotenoid into the film. In contrary to previous reports for individual lipids, we did not observed the aggregation of βC in the mixed lipid monolayer. Moreover, from dilatational rheology experiment we concluded about the significant role of β-carotene in modulation of the elastic behaviour of the membrane, especially in physiologically significant surface pressure, i.e. at π = 30 mN/m.

  • Direct carborane-peptide conjugates: Synthesis and evaluation as non-natural lipopeptide mimetics
    Chem. Phys. Lipids (IF 3.361) Pub Date : 2018-03-29
    Tamara Lützenburg, Ines Neundorf, Matthias Scholz

    Herein, we report the synthesis and characterization of direct carborane-peptide conjugates. Carboranes are non-natural and extremely hydrophobic compounds and turned out to be suitable pharmacophores for diverse biological applications. In this work, we established an efficient procedure for the coupling of carboranes to peptides on solid support. We identified the coupling of carborane-1-carboxylic acids to amino groups to be superior to those with hydroxy- or sulfhydryl-groups. The carborane-peptide conjugates showed remarkably prolonged, and carborane isomer dependent chromatographic retention times. This effect can be used to generate non-natural lipopeptides with fine-tuned properties.

  • 更新日期:2018-03-27
  • Implications of the Mediterranean diet and physical exercise on the lipid profile of metabolically healthy obese women as measured by nuclear magnetic resonance spectroscopy (1H NMR)
    Chem. Phys. Lipids (IF 3.361) Pub Date : 2018-03-23
    Enrique Rodriguez-Garcia, Josefina Ruiz-Nava, Sonia Santamaria-Fernandez, Jose Carlos Fernandez-Garcia, Antonio Vargas Candela, Raquel Yahyaoui, Francisco J. Tinahones, M Rosa Bernal-Lopez, Ricardo Gomez-Huelgas

    Objective There is a lack of consensus when it comes to establishing the biochemical parameters that define metabolically healthy obese (MHO) subjects. Indeed, most studies do not include subjects’ lipid profiles. Our objective was to characterize lipoprotein size, particle and subclass concentration using 1H NMR in MHO women after two years of weight loss with a hypocaloric Mediterranean diet and physical exercise. Methods 115 non-diabetic women (aged 35-55 years) with a body mass index (BMI) of 30–40 kg/m2 and ≤1 of the following criteria: blood pressure ≥135/85 mmHg, fasting plasma glucose ≥100 mg/dL, HDL cholesterol ≤50 mg/dL and triglycerides ≥150 mg/dL were included. After two years of intensive lifestyle modification (Mediterranean diet and physical exercise), they were classified according to their weight loss: <5%, ≥5%-<10% and ≥10%. Lipoprotein size, particle and subclass concentrations were measured using 1H NMR. Results The final population, after dropouts, were 67 women (age: 44.5 ± 3.7 years, BMI: 36.3 ± 4.7 kg/m2), of whom 23 (38.3%) lost <5%, and 22 (36.7%), lost ≥5% to <10% and ≥10% of baseline body weight, respectively. The lipid profile showed no significant changes after intervention, especially in small LDL particles or in production of HDL. The diameter of LDL and HDL particles did not change after two years of a Mediterranean diet and physical exercise. Conclusion These results indicate that intensive lifestyle modification does not produce significant changes in the lipid profile of MHO women. Levels of more atherogenic or atheroprotective particles did not change after two years, despite the intervention.

  • Niemann-Pick C2 protein regulates sterol transport between plasma membrane and late endosomes in human fibroblasts
    Chem. Phys. Lipids (IF 3.361) Pub Date : 2018-03-23
    Zane Berzina, Lukasz M. Solanko, Ahmed S. Mehadi, Maria Louise V. Jensen, Frederik W. Lund, Maciej Modzel, Maria Szomek, Katarzyna A. Solanko, Alice Dupont, Gitte Krogh Nielsen, Christian W. Heegaard, Christer S. Ejsing, Daniel Wüstner

    Niemann-Pick disease type C2 is a lipid storage disorder in which mutations in the NPC2 protein cause accumulation of lipoprotein-derived cholesterol in late endosomes and lysosomes (LE/LYSs). Whether cholesterol delivered by other means to NPC2 deficient cells also accumulates in LE/LYSs is currently unknown. We show that the close cholesterol analog dehydroergosterol (DHE), when delivered to the plasma membrane (PM) accumulates in LE/LYSs of human fibroblasts lacking functional NPC2. We measured two different time scales of sterol diffusion; while DHE rich LE/LYSs moved by slow anomalous diffusion in disease cells (D ∼ 4.6∙10−4 μm2/sec; α∼0.76), a small pool of sterol could exchange rapidly with D ∼ 3 μm2/sec between LE/LYSs, as shown by fluorescence recovery after photobleaching (FRAP). By quantitative lipid mass spectrometry we found that esterification of 13C-labeled cholesterol but not of DHE is reduced 10-fold in disease fibroblasts compared to control cells. Internalized NPC2 rescued the sterol storage phenotype and strongly expanded the dynamic sterol pool seen in FRAP experiments. Together, our study shows that cholesterol esterification and trafficking of sterols between the PM and LE/LYSs depends on a functional NPC2 protein. NPC2 likely acts inside LE/LYSs from where it increases non-vesicular sterol exchange with other organelles.

  • Surface modification of paclitaxel-loaded liposomes using d-α-tocopheryl polyethylene glycol 1000 succinate: Enhanced cellular uptake and cytotoxicity in multidrug resistant breast cancer cells
    Chem. Phys. Lipids (IF 3.361) Pub Date : 2018-03-14
    Su-Min Han, Jong-Suep Baek, Min-Soo Kim, Sung-Joo Hwang, Cheong-Weon Cho

    Liposomes can achieve a controlled release and an improved bioavailability of water- insoluble drug with minimized side effects. Paclitaxel is an efficient anticancer drug for the treatment of various cancers. However, paclitaxel has a solubility of 0.5 mg/L in water and a low bioavailability of 6.5%. Moreover, paclitaxel is a substrate for p-glycoprotein, which shows a decreased accumulation of drug within the cancer cell expressed by a p-glycoprotein. Therefore, the purpose of this study is to prepare a paclitaxel-loaded liposome and evaluate the effect of d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) as an inhibitor of p-glycoprotein on the paclitaxel-loaded liposome. The paclitaxel-loaded liposome and TPGS coated paclitaxel-loaded liposome had spherical vesicles, with mean particle size 184.9 ± 18.45 nm with PDI 0.324 ± 0.018 and 282.6 ± 20.41 nm with PDI 0.269 ± 0.013, respectively. Paclitaxel-loaded liposome and TPGS coated paclitaxel-loaded liposome showed a controlled and sustained release of PTX over 72 hr. The cellular uptake of paclitaxel from TPGS coated paclitaxel-loaded liposome was a 3.56-fold increase for 2 h and 5.75-fold increase for 4 h compared to that from paclitaxel-loaded liposome in MCF-7/ADR cells, resulting in improved cytotoxicity against MCF-7/ADR cells. Western blot assay revealed the P-gp inhibitory effect of TPGS-coated PTX-liposome. In conclusion, TPGS coated liposome with a sustained releasing capability and the inhibitory effect of p-glycoprotein may be a promising carrier for future applications in cancer therapy.

  • Macrophage Sphingolipids are Essential for the Entry of Mycobacteria
    Chem. Phys. Lipids (IF 3.361) Pub Date : 2018-03-08
    Gopinath Viswanathan, Md. Jafurulla, G. Aditya Kumar, Tirumalai R. Raghunand, Amitabha Chattopadhyay
  • Headgroup hydroxylation by OlsE occurs at the C4 position of ornithine lipid and is widespread in proteobacteria and bacteroidetes
    Chem. Phys. Lipids (IF 3.361) Pub Date : 2018-03-07
    Georg Hölzl, Christian Sohlenkamp, Miguel Angel Vences-Guzmán, Nicolas Gisch
  • Antioxidants inhibit low density lipoprotein oxidation less at lysosomal pH: A possible explanation as to why the clinical trials of antioxidants might have failed
    Chem. Phys. Lipids (IF 3.361) Pub Date : 2018-03-05
    Feroz Ahmad, David S. Leake

    Oxidised low density lipoprotein (LDL) was considered to be important in the pathogenesis of atherosclerosis, but the large clinical trials of antioxidants, including the first one using probucol (the PQRST Trial), failed to show benefit and have cast doubt on the importance of oxidised LDL. We have shown previously that LDL oxidation can be catalysed by iron in the lysosomes of macrophages. The aim of this study was therefore to investigate the effectiveness of antioxidants in preventing LDL oxidation at lysosomal pH and also establish the possible mechanism of oxidation. Probucol did not effectively inhibit the oxidation of LDL at lysosomal pH, as measured by conjugated dienes or oxidised cholesteryl esters or tryptophan residues in isolated LDL or by ceroid formation in the lysosomes of macrophage-like cells, in marked contrast to its highly effective inhibition of LDL oxidation at pH 7.4. LDL oxidation at lysosomal pH was inhibited very effectively for long periods by N,N'-diphenyl-1,4-phenylenediamine, which is more hydrophobic than probucol and has been shown by others to inhibit atherosclerosis in rabbits, and by cysteamine, which is a hydrophilic antioxidant that accumulates in lysosomes. Iron-induced LDL oxidation might be due to the formation of the superoxide radical, which protonates at lysosomal pH to form the much more reactive, hydrophobic hydroperoxyl radical, which can enter LDL and reach its core. Probucol resides mainly in the surface monolayer of LDL and would not effectively scavenge hydroperoxyl radicals in the core of LDL. This might explain why probucol failed to protect against atherosclerosis in various clinical trials. The oxidised LDL hypothesis of atherosclerosis now needs to be re-evaluated using different and more effective antioxidants that protect against the lysosomal oxidation of LDL.

  • DPPC Monolayer response to Non-Spanning Cobalt-cage Metallosurfactants: Electrostatic Complex Formation
    Chem. Phys. Lipids (IF 3.361) Pub Date : 2018-02-27
    Lorale J. Lalgee, Leonette Cox, Richard A. Fairman, Lebert Grierson
  • Continuous Detection of Entry of Cell-Penetrating Peptide Transportan 10 into Single Vesicles
    Chem. Phys. Lipids (IF 3.361) Pub Date : 2018-02-06
    Md. Mizanur Rahman Moghal, Md. Zahidul Islam, Sabrina Sharmin, Victor Levadnyy, Md. Moniruzzaman, Masahito Yamazaki
  • 更新日期:2018-02-02
  • Ether-linked lipids: spin-label EPR and spin echoes
    Chem. Phys. Lipids (IF 3.361) Pub Date : 2018-02-02
    Maria Oranges, Rita Guzzi, Derek Marsh, Rosa Bartucci

    Electron spin echo envelope modulation (ESEEM) and conventional electron paramagnetic resonance (EPR) of site-specifically spin-labelled phospholipids are used to investigate the effect of ether-linked chains on the water-penetration and polarity profiles, as well as the phase behaviour and chain flexibility profiles, of phospholipid membranes. D2O-ESEEM reveals that water exposure of the terminal methyl groups in the interdigitated phase of dihexadecyl phosphatidylcholine (DHPC) is comparable to that of the methylene groups at the polar head-group end of the chains. Similarly, an uniform transmembrane polarity profile is obtained from the dependence of the outer 14N-hyperfine splitting on the spin-label position along the chain in frozen interdigitated DHPC dispersions. Two-component conventional EPR spectra of spin labels at the terminal methyl end of the chain reveal that the intermediate gel phase above the pretransition of DHPC contains components in which the lipid chains are interdigitated. The polarity and chain-flexibility profiles in the fluid Lα-phase of DHPC with ether-linked chains are shifted outwards, towards the polar-apolar interface, as compared with that of dihexadecanoyl phosphatidylcholine (DPPC) with ester-linked chains. Also, the polarity profile of DHPC is shifted upwards, to higher polarities. These differences reflect those in hydrocarbon thickness and area/lipid molecule reported by x-ray diffraction for the Lα-phases of the two lipids.

  • On the quantitative phase analysis and amorphous content of triacylglycerols materials by X-ray rietveld method
    Chem. Phys. Lipids (IF 3.361) Pub Date : 2018-01-31
    Guilherme A. Calligaris, Thais L.T. da Silva, Ana Paula B. Ribeiro, Adenilson O. dos Santos, Lisandro P. Cardoso
  • Effects of electroformation protocol parameters on quality of homogeneous GUV populations
    Chem. Phys. Lipids (IF 3.361) Pub Date : 2018-01-31
    Dominik Drabik, Joanna Doskocz, Magda Przybyło
  • Renewable resources-based approach to biantennary glycolipids
    Chem. Phys. Lipids (IF 3.361) Pub Date : 2018-01-31
    Mojtaba Tabandeh, Abbas Abdulameer Salman, Ean Wai Goh, Thorsten Heidelberg, Rusnah Syahila Duali Hussen
  • Rapid Single-step Formation of Liposomes by Flow Assisted Stationary Phase Interdiffusion
    Chem. Phys. Lipids (IF 3.361) Pub Date : 2018-01-31
    Chandra Has, Sopan M. Phapal, P. Sunthar
  • Eicosapentaenoic acid and docosahexaenoic acid have distinct membrane locations and lipid interactions as determined by X-ray diffraction
    Chem. Phys. Lipids (IF 3.361) Pub Date : 2018-01-31
    Samuel C.R. Sherratt, R. Preston Mason

    Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) differentially influence lipid oxidation, signal transduction, fluidity, and cholesterol domain formation, potentially due in part to distinct membrane interactions. We used small angle x-ray diffraction to evaluate the EPA and DHA effects on membrane structure. Membrane vesicles composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and cholesterol (C) (0.3C:POPC mole ratio) were prepared and treated with vehicle, EPA, or DHA (1:10 mole ratio to POPC). Electron density profiles generated from the diffraction data showed that EPA increased membrane hydrocarbon core electron density over a broad area, up to ± 20 Å from the membrane center, indicating an energetically favorable extended orientation for EPA likely stabilized by van der Waals interactions. By contrast, DHA increased electron density in the phospholipid head group region starting at ± 12 Å from the membrane center, presumably due to DHA-surface interactions, with coincident reduction in electron density in the membrane hydrocarbon core centered ± 7–9 Å from the membrane center. The membrane width (d-space) decreased by 5 Å in the presence of vehicle as the temperature increased from 10 °C to 30 °C due to increased acyl chain trans-gauche isomerizations, which was unaffected by addition of EPA or DHA. The influence of DHA on membrane structure was modulated by temperature changes while the interactions EPA were unaffected. The contrasting EPA and DHA effects on membrane structure indicate distinct molecular locations and orientations that may contribute to observed differences in biological activity.

  • Perdeuteration of cholesterol for neutron scattering applications using recombinant Pichia pastoris
    Chem. Phys. Lipids (IF 3.361) Pub Date : 2018-01-31
    Martine Moulin, Gernot A. Strohmeier, Melanie Hirz, Katherine C. Thompson, Adrian R. Rennie, Richard A. Campbell, Harald Pichler, Selma Maric, V. Trevor Forsyth, Michael Haertlein

    Deuteration of biomolecules has a great impact on both quality and scope of neutron scattering experiments. Cholesterol is a major component of mammalian cells, where it plays a critical role in membrane permeability, rigidity and dynamics, and contributes to specific membrane structures such as lipid rafts. Cholesterol is the main cargo in low and high-density lipoprotein complexes (i.e. LDL, HDL) and is directly implicated in several pathogenic conditions such as coronary artery disease which leads to 17 million deaths annually. Neutron scattering studies on membranes or lipid-protein complexes exploiting contrast variation have been limited by the lack of availability of fully deuterated biomolecules and especially perdeuterated cholesterol. The availability of perdeuterated cholesterol provides a unique way of probing the structural and dynamical properties of the lipoprotein complexes that underly many of these disease conditions. Here we describe a procedure for in vivo production of perdeuterated recombinant cholesterol in lipid-engineered Pichia pastoris. Using flask and fed-batch fermenter cultures in deuterated minimal medium perdeuteration of the purified cholesterol was verified by mass spectrometry and its use in a neutron scattering study was demonstrated using neutron reflectometry.

  • Langmuir-Monolayer Methodologies for Characterizing Protein-Lipid Interactions
    Chem. Phys. Lipids (IF 3.361) Pub Date : 2018-01-31
    Mohamed Elderdfi, Aleksander F. Sikorski

    The Langmuir-monolayer technique is a convenient method that allows for continuous control over several membrane-specific parameters, such as molecular packing, physical states, lateral pressure and lipid composition. Lipid monolayers are well suited for applications involving the Langmuir-monolayer technique: they are very well-defined, stable, homogeneous and two-dimensional, and they have planar geometry. In this review, some features of monolayer methodologies based on the Langmuir-monolayer technique are described, with a focus on the step-wise procedures that can be applied to characterize protein-lipid interactions at the lipid monolayer/buffer interface in order to maximize the information concerning the mechanism of interaction between the protein and the lipid monolayer.

  • C24-hydroxylated stigmastane derivatives as Liver X Receptor agonists
    Chem. Phys. Lipids (IF 3.361) Pub Date : 2018-01-17
    Francisco Fermin Castro Navas, Gianluca Giorgi, Daniela Maggioni, Manuela Pacciarini, Vincenzo Russo, Maura Marinozzi

    Phytosterols are stucturally correlated to the endogenous ligands of Liver X Receptor (LXR), a ligand-activated nuclear receptor that has emerged as an attractive drug target due to its ability to integrate metabolic and inflammatory signaling. Natural and semi-synthetic phytosterol derivatives characterized by the presence of side-chain oxygenated functions have shown to be able to modulate LXR activity. Here, we describe the efficient synthesis of four stigmastane derivatives, endowed with a hydroxyl group at C24 position, namely (24R)- and (24S)-stigmasta-5,28-diene-3β,24-ols (also referred to as saringosterols, 10a and 10b) and (24R)- and (24S)-stigmasta-5-ene-3β,24-ols (11a and 11b), starting from the readily available stigmasterol. Thanks to X-ray crystallography the absolute configuration of the newly created chiral centers was definitively assigned for all the four compounds. The subsequent luciferase assays with GAL-4 chimeric receptors evidenced the ability of the two 24(S)-epimers, 10b and 11b, to interact with LXRs, showing the same degree of affinity as (22R)-hydroxycholesterol (1). With regard to the isoform selectivity both the derivatives 10b and 11b showed a preference for LXRβ, up to 4-fold in terms of efficacy for 11b. The gene expression profiling of (24S)-stigmasta-5,28-diene-3β,24-ol (10a) and (24S)-stigmasta-5-ene-3β,24-ol (11a) demonstrated the capability of both the compounds to induce the expression of four well-known LXR target genes, such as ABCA1, SREBP1c, FASN, and SCD1 in U937 monocytic cell line, thus supporting the hypothesis they were LXR positive modulators.

  • 更新日期:2018-01-12
  • Novel lipids with three C18-fatty acid chains and an amino acid head group for pH-responsive and sustained antibiotic delivery
    Chem. Phys. Lipids (IF 3.361) Pub Date : 2018-01-02
    Mahantesh Jadhav, Rahul S. Kalhapure, Sanjeev Rambharose, Chunderika Mocktar, Sanil Singh, Tetsuya Kodama, Thirumala Govender
  • Molecule confirmation and structure characterization of pentatriacontatrienyl mycolate in Mycobacterium smegmatis
    Chem. Phys. Lipids (IF 3.361) Pub Date : 2017-12-30
    Marta Llorens-Fons, Esther Julián, Marina Luquin, Míriam Pérez-Trujillo

    Mycobacterium smegmatis is often used to study the different components of mycobacterial cell wall. Mycolic acids are important components of mycobacterial cell wall that have been associated with virulence. Recently, a novel lipid containing mycolic acids has been described in M. smegmatis. However, some uncertainties regarding the structure of this molecule named mycolate ester wax have been reported. The objective of this work was to perform an in depth structural study of this molecule for its precise characterization. Using 1H and 13C NMR spectroscopy, the molecular structure of mycolate ester wax found in M. smegmatis has been elucidated. The characterization was complemented with MS analyses. This molecule is formed by a carbon chain with three methyl substituted olefinic units and a mycolate structure with trans double bonds and cis cyclopropane rings. The present molecular study will facilitate the detection and identification of pentatriacontatrienyl mycolate in future studies by the performance of a simple 1D 1H NMR experiment.

  • Structural design of intrinsically fluorescent oxysterols
    Chem. Phys. Lipids (IF 3.361) Pub Date : 2017-12-26
    Lina J. Nåbo, Maciej Modzel, Kathiresan Krishnan, Douglas F. Covey, Hideji Fujiwara, Daniel S. Ory, Maria Szomek, Himanshu Khandelia, Daniel Wüstner, Jacob Kongsted

    Oxysterols are oxidized derivatives of cholesterol with many important biological functions. Trafficking of oxysterols in and between cells is not well studied, largely due to the lack of appropriate oxysterol analogs. Intrinsically fluorescent oxysterols present a new route towards direct observation of intracellular oxysterol trafficking by fluorescence microscopy. We characterize the fluorescence properties of the existing fluorescent 25-hydroxycholesterol analog 25-hydroxycholestatrienol, and propose a new probe with an extended conjugated system. The location of both probes inside a membrane is analyzed and compared with that of 25-hydroxycholesterol using molecular dynamics simulations. The analogs’ one- and two-photon absorption properties inside the membrane are evaluated using electronic structure calculations with polarizable embedding. Due to predicted keto–enol tautomerisation of the new oxysterol analog, we also evaluate the keto form. Both analogs are found to be good probe candidates for 25-hydroxycholesterol, provided that the new analog remains in the enol-form. Only the new analog with extended conjugated system shows significant two-photon absorption, which is strongly enhanced by the presence of the membrane.

  • Local Anesthetics Induce Interdigitation and Thermotropic Changes in Dipalmitoylphosphatidylcholine Bilayers
    Chem. Phys. Lipids (IF 3.361) Pub Date : 2017-12-21
    S. Thirupathi Reddy, Sandeep Shrivastava, Amitabha Chattopadhyay
  • Cobalt and Nickel Affect the Fluidity of Negatively-Charged Biomimetic Membranes
    Chem. Phys. Lipids (IF 3.361) Pub Date : 2017-12-13
    Jenelle Umbsaar, Evan Kerek, Elmar J. Prenner
  • Uptake of Iron (III)-Ethylenediamine-N, N, N′, N′-tetraacetic Acid Complex by Phosphatidylcholine Lipid Film Part II. Effect of Film Curvature
    Chem. Phys. Lipids (IF 3.361) Pub Date : 2017-12-11
    Masumi Villeneuve, Mihoko Tanaka, Natsumi Saito, Hiroyasu Sakamoto, Yoshiteru Hayami
  • Phase behavior in the biologically important oleic acid/sodium oleate/water system
    Chem. Phys. Lipids (IF 3.361) Pub Date : 2017-12-02
    Stefania Mele, Olle Söderman, Helena Ljusberg-Wahrén, Krister Thuresson, Maura Monduzzi, Tommy Nylander
  • Ion-induced modification of the sucrose network and its impact on melting of freeze-dried liposomes. DSC and molecular dynamics study
    Chem. Phys. Lipids (IF 3.361) Pub Date : 2017-11-24
    Danijela Bakarić, Dražen Petrov, Yamuna Kunhi Mouvenchery, Stefan Heiβler, Chris Oostenbrink, Gabriele E. Schaumann
  • Mechanical properties of milk sphingomyelin bilayer membranes in the gel phase: Effects of naturally complex heterogeneity, saturation and acyl chain length investigated on liposomes using AFM
    Chem. Phys. Lipids (IF 3.361) Pub Date : 2017-11-22
    Oumaima Et-Thakafy, Nicolas Delorme, Fanny Guyomarc’h, Christelle Lopez

    Sphingomyelin (SM) molecules are major lipid components of plasma membranes that are involved in functional domains. Among natural SMs, that found in milk (milk-SM) exhibits important acyl chain heterogeneities in terms of length and saturation, which could affect the biophysical properties and biological functions of the milk fat globule membrane or of liposome carriers. In this study, the thermotropic and mechanical properties of milk-SM, synthetic C16:0-SM, C24:0-SM and the binary mixtures C16:0-SM/C24:0-SM (50:50% mol) and C24:0-SM/C24:1-SM (95:5% mol) bilayer membranes were investigated using differential scanning calorimetry and atomic force microscopy, respectively. Results showed that acyl chain length, heterogeneity and unsaturation affected i) the temperature of phase transition of SM bilayers, and ii) the mechanical properties of liposome (diameter < 200 nm) membranes in the gel phase, e.g. the Young modulus E and the bending rigidity kC. This study increases our knowledge about the key role of naturally complex lipid compositions in tailoring the physical properties of biological membranes. It could be also used in liposomes development e.g. to select the suitable lipid composition according to usage.

  • The role of caveolin-1 in lipid droplets and their biogenesis
    Chem. Phys. Lipids (IF 3.361) Pub Date : 2017-11-21
    Weria Pezeshkian, Guillaume Chevrot, Himanshu Khandelia

    We address unresolved questions of the energetics and mechanism of lipid droplet (LD) biogenesis, and of the role of caveolins in the endoplasmic reticulum (ER) and in mature LDs. LDs are eukaryotic repositories of neutral lipids, which are believed to be synthesised in the ER. We investigate the effects of a curvature-inducing protein, caveolin-1, on the formation and structure of a spontaneously aggregated triolein (TO) lipid lens in a flat lipid bilayer using molecular dynamics (MD) simulations. A truncated form of caveolin-1 (Cav1) localises on the interface between the spontaneously formed TO aggregate and the bulk bilayer, and thins the bilayer at the edge of the aggregate, which may contribute to lowering the energy barrier for pinching off the aggregate from the host bilayer. Simulations of fully mature LDs do not conclusively establish the optimal localisation of Cav1 in LDs, but when Cav1 is in the LD core, the distribution of both neutral lipids in the LD core, and of phospholipids on the engulfing monolayer are altered significantly. Our simulations provide an unprecedented molecular description of the distribution and dynamics of various lipid species in both mature LDs and in the nascent LD inside the bilayer.

  • Characterization of interactions of eggPC lipid structures with different biomolecules
    Chem. Phys. Lipids (IF 3.361) Pub Date : 2017-11-20
    F. Corrales Chahar, S.B. Díaz, A. Ben Altabef, C. Gervasi, P.E. Alvarez

    In this paper we study the interactions of two biomolecules (ascorbic acid and Annonacin) with a bilayer lipid membrane. Egg yolk phosphatidylcholine (eggPC) liposomes (in crystalline liquid state) were prepared in solutions of ascorbic acid (AA) at different concentration levels. On the other hand, liposomes were doped with Annonacin (Ann), a mono-tetrahydrofuran acetogenin (ACG), which is an effective citotoxic substance. While AA pharmacologic effect and action mechanisms are widely known, those of Ann’s are only very recently being studied. Both Fourier Transformed Infrared (FTIR) and Raman spectroscopic techniques were used to study the participation of the main functional groups of the lipid bilayer involved in the membrane-solution interaction. The obtained spectra were comparatively analyzed, studying the spectral bands corresponding to both the hydrophobic and the hydrophilic regions in the lipid bilayer. Electrochemical experiments namely; impedance spectroscopy (EIS) and cyclic voltamperometry (CV) were used as the main characterization techniques to analyse stability and structural changes of a model system of supported EggPC bilayer in connection with its interactions with AA and Ann. At high molar ratios of AA, there is dehydration in both populations of the carbonyl group of the polar head of the lipid. On the other hand, Ann promotes the formation of hydrogen bonds with the carbonyl groups. No interaction between AA and phosphate groups is observed at low and intermediate molar ratios. Ann is expected to be able to induce the dehydration of the phosphate groups without the subsequent formation of H bonds with them. According to the electrochemical analysis, the interaction of AA with the supported lipid membrane does not alter its dielectric properties. This fact can be related to the conservation of structured water of the phosphate groups in the polar heads of the lipid. On the other hand, the incorporation of Ann into the lipid membrane generates an increase in the number of defects while changes the dielectric constant. This, in turn, can be associated with the induced dehydration of the phosphate groups.

  • IR spectroscopy analysis of pancreatic lipase-related protein 2 interaction with phospholipids: 2. Discriminative recognition of various micellar systems and characterization of PLRP2-DPPC-bile salt complexes
    Chem. Phys. Lipids (IF 3.361) Pub Date : 2017-11-16
    Eduardo Mateos-Diaz, Priscila Sutto-Ortiz, Moulay Sahaka, Deborah Byrne, Hélène Gaussier, Frédéric Carrière

    The interaction of pancreatic lipase-related protein 2 (PLRP2) with various micelles containing phospholipids was investigated using pHstat enzyme activity measurements, differential light scattering, size exclusion chromatography (SEC) and transmission IR spectroscopy. Various micelles of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and lysophosphatidylcholine were prepared with either bile salts (sodium taurodeoxycholate or glycodeoxycholate) or Triton X-100, which are substrate-dispersing agents commonly used for measuring phospholipase activities. PLRP2 displayed a high activity on all phospholipid-bile salt micelles, but was totally inactive on phospholipid-Triton X-100 micelles. These findings clearly differentiate PLRP2 from secreted pancreatic phospholipase A2 which is highly active on both types of micelles. Using an inactive variant of PLRP2, SEC experiments allowed identifying two populations of PLRP2-DPPC-bile salt complexes corresponding to a high molecular weight 1:1 PLRP2-micelle association and to a low molecular weight association of PLRP2 with few monomers of DPPC/bile salts. IR spectroscopy analysis showed how DPPC-bile salt micelles differ from DPPC-Triton X-100 micelles by a higher fluidity of acyl chains and higher hydration/H-bonding of the interfacial carbonyl region. The presence of bile salts allowed observing changes in the IR spectrum of DPPC upon addition of PLRP2 (higher rigidity of acyl chains, dehydration of the interfacial carbonyl region), while no change was observed with Triton X-100. The differences between these surfactants and their impact on substrate recognition by PLRP2 are discussed, as well as the mechanism by which high and low molecular weight PLRP2-DPPC-bile salt complexes may be involved in the overall process of DPPC hydrolysis.

  • IR spectroscopy analysis of pancreatic lipase-related protein 2 interaction with phospholipids: 3. Monitoring DPPC lipolysis in mixed micelles
    Chem. Phys. Lipids (IF 3.361) Pub Date : 2017-11-11
    Eduardo Mateos-Diaz, Priscila Sutto-Ortiz, Moulay Sahaka, Jorge A. Rodriguez, Frédéric Carrière

    Usual methods for the continuous assay of lipolytic enzyme activities are mainly based on the titration of free fatty acids, surface pressure monitoring or spectrophotometry using substrates labeled with specific probes. These approaches only give a partial information on the chemistry of the lipolysis reaction and additional end-point analyses are often required to quantify both residual substrate and lipolysis products. We used transmission infrared (IR) spectroscopy to monitor simultaneously the hydrolysis of phospholipids by guinea pig pancreatic lipase-related protein 2 (GPLRP2) and the release of lipolysis products. The substrate (DPPC, 1,2-Dipalmitoyl phosphatidylcholine) was mixed with sodium taurodeoxycholate (NaTDC) to form mixed micelles in D2O buffer at pD 6 and 8. After hydrogen/deuterium exchange, DPPC hydrolysis by GPLRP2 (100 nM) was monitored at 35 °C in a liquid cell by recording IR spectra and time-course variations in the CO stretching region. These changes were correlated to variations in the concentrations of DPPC, lysophospholipids (lysoPC) and palmitic acid (Pam) using calibration curves established with these compounds individually mixed with NaTDC. We were thus able to quantify each compound and its time-course variations during the phospholipolysis reaction and to estimate the enzyme activity. To validate the IR analysis, variations in residual DPPC, lysoPC and Pam were also quantified by thin-layer chromatography coupled to densitometry and similar hydrolysis profiles were obtained using both methods. IR spectroscopy can therefore be used to monitor the enzymatic hydrolysis of phospholipids and obtain simultaneously chemical and physicochemical information on substrate and all reaction products (H-bonding, hydration, acyl chain mobility).

  • The lipolytic degradation of highly structured cubic micellar nanoparticles of soy phosphatidylcholine and glycerol dioleate by phospholipase A2 and triacylglycerol lipase
    Chem. Phys. Lipids (IF 3.361) Pub Date : 2017-11-11
    Maria Wadsäter, Justas Barauskas, Fredrik Tiberg, Tommy Nylander

    The effects of different lipolytic enzymes on the structure of lipid liquid crystalline nano-particles (LCNP) have been investigated by cryogenic transmission electron microscopy (cryo-TEM) and synchrotron small angle X-ray diffraction (SAXD). Here we used highly structured cubic micellar (Fd3m) nanoparticles of 50/50 (wt%/wt%) soy phosphatidyl choline (SPC)/glycerol dioleate (GDO) as substrate. Two types of lipolytic enzymes were used, phospholipase A2 (PLA2) that catalyses degradation of the phospholipid component, SPC, and porcine pancreatic triacylglycerol lipase (TGL) that facilitate the hydrolysis of the diglyceride, GDO. Evolution of the structure was found to be very different and linked to specificity of the two types of enzymes. PLA2, which hydrolyses the lamellar forming component, SPC, induces a reversed micellar lipid phase, while TGL which hydrolysis the reverse phase forming compound, GDO, induces a lamellar phase.

  • The triolein/aqueous interface and lipase activity studied by spectroscopic ellipsometry and coarse grained simulations
    Chem. Phys. Lipids (IF 3.361) Pub Date : 2017-11-10
    Arne Stamm, Allan Svendsen, Jakob Skjold-Jørgensen, Thomas Vissing, Ida Berts, Tommy Nylander

    In spite of the importance of the triglyceride aqueous interface for processes like emulsification, surfactant interactions and lipase activity, relatively little is known about this interface compared to that between alkanes and water. Here, the contact between triolein and water was investigated in terms of water inclusion in the oil phase and orientation of the molecules at the interface. Coarse grained models of triglycerides in contact with water were constructed and correlated with experimental results of the changes in thickness and refractive index, obtained using spectroscopic ellipsometry of spin-coated triolein films. The topography of the layer was revealed by atomic force microscopy. Dry triolein and a triolein sample after equilibration with water were also compared structurally using small-angle X-ray scattering. Additionally, the kinetics of adsorption/activity of three different variants of the Thermomyces lanuginosus lipase (TLL) were investigated. The results show that uptake of water in the triolein phase leads to increase in thickness of the layer. The observed increase of thickness was further enhanced by an active lipase but reduced when an inactive mutant of the enzyme was applied.

  • Poly (vinyl pyrrolidone)-lipid based hybrid nanoparticles for anti viral drug delivery
    Chem. Phys. Lipids (IF 3.361) Pub Date : 2017-11-10
    K.S. Joshy, S. Snigdha, George Anne, Kalarikkal Nandakumar, Pothen Laly. A., Thomas Sabu

    Zidovudine (AZT) is an antiviral drug with moderate solubility in water. It has limited application due to its short half life in vivo and consequent requirement for frequent administrations. To solve this problem, zidovudine loaded polyvinylpyrrolidone (PVP)/stearic acid (SA)-polyethylene glycol (PEG) nanoparticles (PSNPs) were developed.The hybrid nanoparticles were prepared by emulsification–solvent evaporation method. The physico chemical characterizations of the PSNPs was done by dynamic light scattering (DLS), transmission electron microscopy (TEM), and fourier transform infra-red spectroscopy (FT-IR). The in vitro release behavior and haemocompatibility studies were also performed. The in vitro cytotoxicity and cell uptake studies of the PSNPs were assessed in murine neuro-2a and HeLa cells. Our results revealed that the core shell PSNPs prepared from lipid and polymer led to significant improvement in cellular internalization. Therefore, it is envisaged that nanoparticles composed of lipid and polymer moieties may constitute a preferred embodiment for anti-viral drug delivery for use in HIV/AIDS therapy.

  • Photo-triggered recognition between host and guest compounds in a giant vesicle encapsulating photo-pierceable vesicles
    Chem. Phys. Lipids (IF 3.361) Pub Date : 2017-11-09
    Kentaro Suzuki, Kotaro Machida, Kazuo Yamaguchi, Tadashi Sugawara

    Here, we used centrifugal precipitation to construct a giant vesicle (GV) encapsulating smaller giant vesicles (GV-in-GV) which comprises a photo-resistant outer GV and a photo-pierceable inner GV; the outer GV contained a fluorescent probe (SYBR Green I) in its inner water pool, and the inner GV contained double-stranded DNA (dsDNA) in its inner water pool. The phospholipid membrane of the inner GV was made photo-pierceable by inclusion of ca. 15 mol% of a caged phospholipid in its membrane. Immediately after exposure of the GV-in-GVs to UV irradiation, strong fluorescence was detected in the inner water pool of the outer GV, indicating that dsDNA had been released from the inner GV and had complexed with the fluorescent probe. These dynamics can be recognized as a macroscopic representation of the molecular level function of a caged compound.

  • N-Docosahexaenoylethanolamine (synaptamide): Carbon-14 radiolabeling and metabolic studies
    Chem. Phys. Lipids (IF 3.361) Pub Date : 2017-11-08
    Shilpa Sonti, Richard I. Duclos, Mansi Tolia, Samuel J. Gatley

    N-Docosahexaenoylethanolamine (synaptamide) is structurally similar to the endocannabinoid N-arachidonoylethanolamine (anandamide), but incorporates the omega-3 22:6 fatty acid docosahexaenoic acid (DHA) in place of the omega-6 20:4 fatty acid arachidonic acid (AA). Some brain membrane lipid effects may be mediated via synaptamide. In competition experiments with mouse brain homogenate in vitro, we found that synaptamide was an order-of-magnitude poorer inhibitor of radioactive anandamide hydrolysis than was anandamide itself. Also, enzyme-mediated hydrolysis of synaptamide was observed to occur at a slower rate than for anandamide. We have synthesized synaptamide radiolabeled with carbon-14 in both the ethanolamine ([α,β-14C2]synaptamide) and in the DHA ([1-14C]synaptamide) moieties. The brain penetration, distribution, and metabolism of radiolabeled synaptamide were studied in mice in vivo relative to anandamide, DHA, and AA. Brain uptake of labeled synaptamide was greater than for labeled DHA, consistent with previous studies of labeled anandamide and AA in our laboratory. After administering either isotopomer of radiolabeled synaptamide, radiolabeled phospholipids were found in mouse brain. Pretreatment of mice with PF3845, a potent, specific inhibitor of fatty acid amide hydrolase (FAAH), eliminated formation of labeled phospholipids measured after 15 min, suggesting that synaptamide is hydrolyzed nearly exclusively by FAAH, though it is a poorer substrate for FAAH than anandamide.

  • Role of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) in β-lactoglobulin aggregation
    Chem. Phys. Lipids (IF 3.361) Pub Date : 2017-11-08
    Baoliang Ma, Xiaofei Wang, Yujie Liu, Zhihong Li, Fan Zhang

    Protein aggregation is a prevalent phenomenon. It is important to study protein aggregation under different solution conditions. In this study, using 1-anilinonaphthalene-8-sulfonic acid (ANS) fluorescence spectra, we investigated the critical micelle concentration (CMC) of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP). We also studied the effects of DOTAP on amyloid aggregation of β-lactoglobulin using intrinsic fluorescence spectra, circular dichroism spectra, thioflavin T fluorescence, a Congo red binding assay and transmission electron microscopy. We observed that DOTAP had a dual role on β-lactoglobulin amyloid aggregation. DOTAP inhibited the amyloid aggregation below the CMC, while it had the opposite effect above the CMC. Moreover, the results of transmission electron microscopy showed that spherical aggregates were formed above the CMC. These results led us to conclude that cationic lipids could be used as modulators of protein self-assembly.

  • MALDI imaging of enzymatic degradation of glycerides by lipase on textile surface
    Chem. Phys. Lipids (IF 3.361) Pub Date : 2017-11-06
    Jonatan Hall-Andersen, Svend G. Kaasgaard, Christian Janfelt

    Most modern laundry detergents contain enzymes such as proteases, amylases, and lipases for more efficient removal of stains containing proteins, carbohydrates, and lipids during wash at low temperature. The function of the lipases is to hydrolyse the hydrophobic triglycerides from fats and oils to the more hydrophilic lipids diglycerides, monoglycerides and free fatty acids. Here, we use MALDI imaging to study the effect of enzymatic degradation of triglycerides by lipases directly on the textile surface. Textile samples were created by using swatches of different textile blends, adding a lipid stain and simulating washing cycles using well-defined detergents with lipase concentrations ranging between 0 and 0.5 ppm. After washing, the textile swatches as well as cryo-sections of the swatches were imaged using MALDI imaging in positive ion mode at pixel sizes of 15–75 μm. Similar samples were imaged by DESI-MSI for comparison. Despite the rough surface and non-conductive nature of textile, MALDI imaging of glycerides on textile was readily possible. The results show extensive enzymatic degradation of triglycerides into diglycerides, and images suggest that this degradation takes place in a quite heterogeneous manner as also observed in images of cross-sections. DESI-imaging reveals the same kind of enzymatic degradation, but with a more homogeneous appearance. While the enzymatic degradation is exemplified in a few images, the overall degradations process was monitored by extraction of ion intensities from 298 individual ion masses of mono-, di- and triglycerides and free fatty acids. MALDI imaging of glycerides was possible directly from a textile surface, allowing visualization of the enzymatic degradation of fatty stains on textile during the laundry process. The images showed an inhomogeneous presence of diglycerides after lipase treatment both in planar images of the textile surface as well as in cross-sections suggesting a non-uniform enzyme effect or extraction of the lipase reaction products from the textile.

  • Microfluidic device as a facile in vitro tool to generate and investigate lipid gradients
    Chem. Phys. Lipids (IF 3.361) Pub Date : 2017-11-02
    Brittany M. Neumann, Devin Kenney, Qi Wen, Arne Gericke

    This work describes a method that utilizes a microfluidic gradient generator to develop lateral lipid gradients in supported lipid bilayers (SLB). The new methodology provides freedom of choice with respect to the lipid composition of the SLB. In addition, the device has the ability to create a protein or bivalent cation gradient in the aqueous phase above the lipid bilayer which can elicit a gradient specific response in the SLB. To highlight these features we demonstrate that we can create a phosphoinositide gradient on various length scales, ranging from 2 mm to 50 μm. We further show that a Ca2+ gradient in the aqueous phase above the SLB causes anionic lipid clustering mirroring the cation gradient. We demonstrate this effect for mixed phosphatidylcholine/phosphatidylinositol-4,5-bisphosphate bilayers and fora mixed phosphatidylcholine/phosphatidylserine bilayers. The biomimetic platform can be combined with a Total Internal Reflection Fluorescence (TIRF) microscopy setup, which allows for the convenient observation of the time evolution of the gradient and the interaction of ligands with the lipid bilayer. The method provides unprecedented access to study the dynamics and mechanics of protein-lipid interactions on membranes with micron level gradients, mimicking plasma membrane gradients observed in organisms such as Dictyostelium discodeum and neutrophils.

  • The interaction of phospholipase A2 with oxidized phospholipids at the lipid-water surface with different structural organization
    Chem. Phys. Lipids (IF 3.361) Pub Date : 2017-10-31
    N.M. Litvinko, L.A. Skorostetskaya, D.O. Gerlovsky

    Phospholipase A2 (PLA2 IB) activity towards UV-irradiated (λ = 180–400 nm) phospholipids in comparison to non-irradiated ones was investigated using phosphatidylcholine (PC) liposomes and mixed micelles of phosphatidylcholine and sodium deoxycholate as a membrane model. PLA2 activity, determined by spectral changes of hemoglobin (Hb) under the interaction with fatty acids (product of the phospholipolysis), correlated well with the phospholipid peroxidation degree. The present work is the first study that determines the degree of oxidation of non-fragmented OxPCs, on the base of PLA2 activity. Fragmented OxPLs have been determined as usually by analysis of MDA using spectroscopy at 532 nm. Antioxidant Trolox and human blood serum reduced observed exceeding of PLA2 activity toward OxPLs, what makes this model perspective for determining the total antioxidant activity of biological liquids.

  • A closer look at the behaviour of milk lipids during digestion
    Chem. Phys. Lipids (IF 3.361) Pub Date : 2017-10-31
    Andrew J. Clulow, Malinda Salim, Adrian Hawley, Ben J. Boyd

    Milk has recently been reported to form complex self-assembled liquid crystalline structures during digestion by lipolytic enzymes. The formation of cubic phases at the endpoint of digestion was of particular interest as this requires a fine balance in self-assembly. This manuscript probes the robustness of the kinetic structural behaviour when milk is subjected to a range of processes that are encountered by milk and/or are relevant to the use of milk in pharmaceutical applications (homogenisation, lyophilisation, freeze-thawing and freeze-drying) using time-resolved small angle X-ray scattering (TR-SAXS). The nature of the persistent lamellar phase that occurs during digestion is elucidated using SAXS and X-ray photoelectron spectroscopy, and the interplay between the formation of structured mesophases and the evolution of particle size during digestion is determined using laser light scattering studies. This closer look at milk lipids during digestion establishes the dependence of the structural behaviour of milk on lipid composition and not processing, and clarifies the phase behaviour and kinetic effects on particle size distribution under lipolytic conditions.

  • Fliposomes: trans-2-aminocyclohexanol-based amphiphiles as pH-sensitive conformational switches of liposome membrane – a structure-activity relationship study
    Chem. Phys. Lipids (IF 3.361) Pub Date : 2017-10-28
    Yu Zheng, Xin Liu, Nataliya M. Samoshina, Vyacheslav V. Samoshin, Andreas H. Franz, Xin Guo

    Recently developed lipids with the trans-2-aminocyclohexanol (TACH) moiety represent unique pH-sensitive conformational switches (“flipids”) that can trigger the membrane of liposome-based drug delivery systems at lowered pH as seen in many pathological scenarios. A library of flipids with various TACH-based headgroups and hydrocarbon tails were designed, prepared, and characterized to systematically elucidate the relationship between their chemical structures and their ability to form and to trigger liposomes. Liposomes (fliposomes) consisting of a flipid, POPC and PEG-ceramide were stable at 4 °C, pH 7.4 for up to several months and yet released the encapsulated fluorophore in seconds upon acidification. The colloidal properties and encapsulation efficiencies of the fliposomes depended on the structure features of the flipids such as the polarity of the headgroups and the shape and fluidity of the lipid tails. The pH-triggered release also depended on the flipid structure, where shorter linear tails yielded more efficient release. The release of fliposomes was enhanced at different narrow pH ranges, depending on the basicity of the flipid headgroup, which can be estimated either by calculated pKa or by acid/base titration of the flipids while its conformation is monitored by 1H NMR. The structure-activity relationship of the flipids supports “lipid tail conformational shortening” as the mechanism to disrupt lipid membranes and would provide great flexibility in the design of pH-sensitive drug delivery systems.

  • The effect of membrane softeners on rigidity of lipid vesicle bilayers: Derivation from vesicle size changes
    Chem. Phys. Lipids (IF 3.361) Pub Date : 2017-10-28
    Mustafa M.A. Elsayed, Marwa M. Ibrahim, Gregor Cevc

    Deformability is not just a fundamentally interesting vesicle characteristic; it is also the key determinant of vesicle ability to cross the skin barrier; i.e. skin penetrability. Development of bilayer vesicles for drug and vaccine delivery across the skin should hence involve optimization of this property, which is controllable by the concentration of bilayer softeners in or near the vesicle bilayers. To this end, we propose a simple method for quantifying the effect of bilayer softeners on deformability of bilayer vesicles. The method derives the bending rigidity of vesicle bilayers from vesicle size dependence on softener concentration. To exemplify the method, we studied mixtures of soybean phosphatidylcholine with anionic sodium deoxycholate, non-ionic polyoxyethylene (20) sorbitan oleyl ester (polysorbate 80), or non-ionic polyoxyethylene (20) oleyl ether (C18:1EO20, Brij® 98). With each of the tested bilayer softeners, the bending rigidity of the resulting mixed-amphipat vesicle bilayers decreased quasi-exponentially as the concentration of the bilayer softener increased, as one would expect on theoretical ground. The bilayer bending rigidity reached low values, near the thermal stability limit, i.e. kBT, before vesicle transformation into non-vesicular aggregates began. For a soybean phosphatidylcholine concentration of 5.0 mmol kg−1, the bilayer bending rigidity reached 1.5 kBT at the total deoxycholate concentration of 4.1 mmol kg−1 and 3.4 kBT at the total polysorbate 80 concentration of 2.0 mmol kg−1. In the case of C18:1EO20, the bilayer bending rigidity reached 1.5 kBT at the bilayer surface occupancy α = 0.1. The dependence of vesicle size on bilayer softener concentration thus reveals vesicle transformation into different aggregate structures (such as mixed micelles with poor skin penetrability) and practically valuable information on vesicle deformability. Our results compare favorably with results of literature measurements. We provide practical guidance on using the new analytical method to optimize deformable vesicle formulations.

  • Shipment of a photodynamic therapy agent into model membrane and its controlled release: A photophysical approach
    Chem. Phys. Lipids (IF 3.361) Pub Date : 2017-10-19
    Monaj Karar, Suvendu Paul, Arabinda Mallick, Tapas Majumdar

    Harmine, an efficient cancer cell photosensitizer (PS), emits intense violet color when it is incorporated in well established self assembly based drug carrier formed by cationic surfactants of identical positive charge of head group but varying chain length, namely, dodecyltrimethylammonium bromide (DTAB), tetradecyltrimethylammonium bromide (TTAB) and cetyltrimethylammonium bromide (CTAB). Micelle entrapped drug emits in the UV region when it interacts with non-toxic β-cyclodextrin (β-CD). Inspired by these unique fluorescence/structural switching properties of the anticancer drug, in the present work we have monitored the interplay of the drug between micelles and non-toxic β-CDs. We have observed that the model membranes formed by micelles differing in their hydrophobic chain length interact with the drug differently. Variation in the surfactant chain length plays an important role for structural switching i.e. in choosing a particular structural form of the drug that will be finally presented to their targets. The present study shows that in case of necessity, the bound drug molecule can be removed from its binding site in a controlled manner by the use of non-toxic β-CD and it is exploited to serve a significant purpose for the removal of excess/unused adsorbed drugs from the model cell membranes. We believe this kind of β-CD driven translocation of drugs monitored by fluorescence switching may find possible applications in controlled release of the drug inside cells.

Some contents have been Reproduced with permission of the American Chemical Society.
Some contents have been Reproduced by permission of The Royal Society of Chemistry.
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