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  • 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.

  • Membrane-induced organization and dynamics of the N-terminal domain of chemokine receptor CXCR1: insights from atomistic simulations
    Chem. Phys. Lipids (IF 3.361) Pub Date : 2017-09-20
    Shalmali Kharche, Manali Joshi, Durba Sengupta, Amitabha Chattopadhyay

    The CXC chemokine receptor 1 (CXCR1) is an important member of the G protein-coupled receptor (GPCR) family in which the extracellular N-terminal domain has been implicated in ligand binding and selectivity. The structure of this domain has not yet been elucidated due to its inherent dynamics, but experimental evidence points toward membrane-dependent organization and dynamics. To gain molecular insight into the interaction of the N-terminal domain with the membrane bilayer, we performed a series of microsecond time scale atomistic simulations of the N-terminal domain of CXCR1 in the presence and absence of POPC bilayers. Our results show that the peptide displays a high propensity to adopt a β-sheet conformation in the presence of the membrane bilayer. The interaction of the peptide with the membrane bilayer was found to be transient in our simulations. Interestingly, a scrambled peptide, containing the same residues in a randomly varying sequence, did not exhibit membrane-modulated structural dynamics. These results suggest that sequence-dependent electrostatics, modulated by the membrane, could play an important role in folding of the N-terminal domain. We believe that our results reinforce the emerging paradigm that cellular membranes could be important modulators of function of G protein-coupled receptors such as CXCR1.

  • Non-natural lipids: Synthesis and characterization of esters from meta-carborane-1-carboxylic acid
    Chem. Phys. Lipids (IF 3.361) Pub Date : 2017-09-01
    Dhilan C. Tribovane, Matthias S. Scholz

    Lipids are defined as apolar molecules comprising as major classes fatty acids and fatty acid esters of normally natural origin. Non-natural components, such as dicarba-closo-dodecaboranes (in short carboranes) can also form acids and esters, which reveal lipid-like properties. Carboranes are synthetic boron clusters featuring ten BH and two CH vertices, organized in icosahedral shape. The highly hydrophobic clusters are organic-inorganic hybrid constructs and can be modified at both the cluster boron and the cluster carbon atoms via adjusted organic reactions. Here, we report the synthesis and characterization of lipid esters from meta-carborane-1-carboxylic acid using a new coupling reagent strategy. Carboranyl esters from long-chain alcohols revealed wax-like properties.

  • The effect of mutations in the lid region of Thermomyces lanuginosus lipase on interactions with triglyceride surfaces: A multi-scale simulation study
    Chem. Phys. Lipids (IF 3.361) Pub Date : 2017-08-15
    Nathalie Willems, Mickäel Lelimousin, Jakob Skjold-Jørgensen, Allan Svendsen, Mark S.P. Sansom

    Lipases naturally function at the interface formed between amphiphilic molecules and the aqueous environment. Thermomyces lanuginosus lipase (TLL) is a well-characterised lipase, known to exhibit interfacial activation during which a lid region covering the active site becomes displaced upon interaction with an interface. In this study, we investigate the effect the amino acid sequence of the lid region on interfacial binding and lid dynamics of TLL. Three TLL variants were investigated, a wild-type variant, a variant containing an esterase lid region (Esterase), and a Hybrid variant, containing both wild-type lid residues and esterase lid residues. Multiple coarse-grained molecular dynamics simulations revealed that the interfacial binding orientation of TLL was significantly affected by the nature of amino acids in the lid region, and atomistic simulations indicated effects on the structural dynamics of the lid itself. The atomistic simulations, as well as steered molecular dynamics simulations, also indicated that the Esterase lid region was less flexible than the wild-type lid region, whereas the Hybrid variant displayed superior lid flexibility and stability in the open conformation both at the interface, and in aqueous solution. Additional experiments performed to investigate the activity and binding behaviour of the lipase variants indicated a slightly higher specific activity for the Hybrid variant compared to the wild-type variant, correlating the observations of increased lid flexibility. Together, these results are in line with previous experimental studies, highlighting the importance of the nature of the amino acid residues within the functional lid region of lipases, particularly regarding interfacial binding orientation, activation, and structural stability.

  • Efficient heterologous expression, functional characterization and molecular modeling of annular seabream digestive phospholipase A2
    Chem. Phys. Lipids (IF 3.361) Pub Date : 2017-06-15
    Nabil Smichi, Houcemeddine Othman, Neila Achouri, Alexandre Noiriel, Soumaya Triki, Vincent Arondel, Najet Srairi-abid, Abdelkarim Abousalham, Youssef Gargouri, Nabil Miled, Ahmed Fendri

    Here we report the cDNA cloning of a phospholipase A2 (PLA2) from five Sparidae species. The deduced amino acid sequences show high similarity with pancreatic PLA2. In addition, a phylogenetic tree derived from alignment of various available sequences revealed that Sparidae PLA2 are closer to avian PLA2 group IB than to mammals’ ones. In order to understand the structure-function relationships of these enzymes, we report here the recombinant expression in E.coli, the refolding and characterization of His-tagged annular seabream PLA2 (AsPLA2). A single Ni-affinity chromatography step was used to obtain a highly purified recombinant AsPLA2 with a molecular mass of 15 kDa as attested by gel electrophoresis and MALDI-TOF mass spectrometry data. The enzyme has a specific activity of 400 U.mg−1 measured on phosphatidylcholine at pH 8.5 and 50 °C. The enzyme high thermo-activity and thermo-stability make it a potential candidate in various biological applications. The 3D structure models of these enzymes were compared with structures of phylogenetically related pancreatic PLA2. By following these models and utilizing molecular dynamics simulations, the resistance of the AsPLA2 at high temperatures was explained. Using the monomolecular film technique, AsPLA2 was found to be active on various phospholipids spread at the air/water interface at a surface pressure between 12 and 25 dyn cm−1. Interestingly, this enzyme was shown to be mostly active on dilauroyl-phosphatidylglycerol monolayers and this behavior was confirmed by molecular docking and dynamics simulations analysis. The discovery of a thermo-active new member of Sparidae PLA2, provides new insights on structure-activity relationships of fish PLA2.

  • IR spectroscopy analysis of pancreatic lipase-related protein 2 interaction with phospholipids: 1. Discriminative recognition of mixed micelles versus liposomes
    Chem. Phys. Lipids (IF 3.361) Pub Date : 2017-02-21
    Eduardo Mateos-Diaz, Jean-Claude Bakala N’Goma, Deborah Byrne, Sylvie Robert, Frédéric Carrière, Hélène Gaussier

    Guinea pig pancreatic lipase-related protein 2 (GPLRP2) is an interesting model enzyme that can hydrolyze a large set of acylglycerols in vitro but displays however some selectivity depending on the supramolecular structure of substrate and the presence of surfactants like bile salts. We showed that GPLRP2 hydrolyzes 1,2-dipalmitoyl phosphatidylcholine (DPPC) present in mixed micelles with sodium taurodeoxycholate (NaTDC) but not in multilamellar (MLV) and large unilamellar (LUV) vesicles of DPPC. After characterization of these lipid aggregates by dynamic light scattering (DLS), the discriminative recognition of DPPC in DPPC/NaTDC micelles versus MLV and LUV by an inactive variant (S152G) of GPLRP2 to avoid the effect of substrate hydrolysis was investigated using Fourier transform infrared spectroscopy (FTIR). IR spectra were recorded after hydrogen/deuterium exchange, at pD 6 and various temperatures to study phase transitions. We analyzed the methylene asymmetric stretching (ν(CH2)as), the carbonyl stretching (ν(CO)) and the composite polar head-group vibration bands, first to characterized differences in DPPC micelles and vesicles, and second to estimate the degree of interaction of GPLRP2 S152G with phospholipid. Our results indicate that a significant interaction between GPLRP2 S152G and DPPC is only observed when NaTDC is added to the system to form micelles and this can be explained by the different organization of DPPC in mixed micelles compared to lamellar vesicles (higher hydration of polar head, higher mobility of alkyl chains) that favors GPLRP2 penetration into the phospholipid layer.

  • Uptake of Iron (III)-Ethylenediamine-N,N,N′,N′-tetraacetic Acid Complex by Phosphatidylcholine Lipid Film Part I. Effect of Bulk pH
    Chem. Phys. Lipids (IF 3.361) Pub Date : 2017-12-06
    Masumi Villeneuve, Mihoko Tanaka, Natsumi Saito, Hiroyasu Sakamoto, Yoshiteru Hayami

    We studied a ternary solutes aqueous solution of NaOH, iron (III)-ethylenediamine-N,N,N′,N′-tetraacetic acid complex (Fe-edta), and 1,2-diheptanoyl-sn-glycero-3-phosphatidylcholine (DHPC)/air interface system to clarify the interactions between iron complexes and lipids with a phosphatidylcholine head group. The solution surface tension and pH were measured as functions of the total molality of NaOH, Fe-edta and DHPC, and the mole fractions of NaOH and DHPC. Rigorous thermodynamic equations were derived, in which the overall proton dissociation equilibria of Fe-edta and DHPC were taken into consideration, and applied to experimental data to obtain phase diagram of adsorption. It was found that (1) adsorption of Fe-edta at the solution/air interface with a DHPC monolayer was about 50 to 130 times higher than that without a DHPC monolayer and (2) when the bulk mole fraction of NaOH was high, Fe-edta tended to be expelled from the adsorbed film. The last finding suggests that the ambient pH significantly affects passive transport of the iron complex through a phospholipid-containing membrane into the cell interior.

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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