SciCombinator

Discover the most talked about and latest scientific content & concepts.

Journal: Chemistry and physics of lipids

27

Presence of sialic acid distinguishes gangliosides from other glycosphingolipids, helps maintain membrane structure and organization as well as acts as anchors for lectins, toxins and pathogens. The number and position of the sialic acid residues on gangliosides appear to influence the binding affinity and specificity of gangliosides. We have investigated the dependence of bicellar properties on sialic acids using Monosialo1 (GM1), Disialo1b (GD1b) and Trisialo1a (GT1a) gangliosides incorporated in phospholipid bicelles. TEM, AFM and DLS show that increasing numbers of sialic acid moieties per ganglioside results in an increase in bicelle size. DPH fluorescence anisotropy results suggest that with incorporation of gangliosides in bicelles the orientational order of the hydrocarbon chains increases. Fluorescence anisotropy was used to explore the effect of gangliosides on lateral phase separation in ganglioside enriched bicelles. GM1 and GT1a exhibited a low Tm melting domain (DMPC rich) and a high Tm melting domain (ganglioside rich). For GD1b containing bicelles, no significant phase separation was observed, suggesting a single homogeneous phase. Symmetric and antisymmetric stretching vibrational bands of methylene shift to a lower wave number, implying acyl chain order decreasing as GT1a≪GM1

Concepts: Cell membrane, Sialic acid, Wave, Glycoprotein, Ganglioside, Grammatical number, Cholera toxin, GM1

26

Bcl-2 family proteins are involved in cell homeostasis, where they regulate cell death. Some of these proteins are pro-apoptotic and others pro-survival. Moreover, many of them share a similar domain composition with several of the so-called BH domains, although some only have a BH3 domain. A C-terminal domain is present in all the multi-BH domain proteins and in some of the BH3-only ones. This C-terminal domain is hydrophobic or amphipathic, for which reason it was thought when they were discovered that they were membrane anchors. Although this is indeed one of their functions, it has since been observed that they may also serve as regulators of the function of some members of this family, such as Bax. They may also serve to recognize the target membrane of some of these proteins, which only after an apoptotic signal, are incorporated into a membrane. It has been shown that peptides that imitate the sequence of C-terminal domains can form pores and may serve as a model to design cytotoxic molecules.

Concepts: Protein, Protein structure, Apoptosis, Programmed cell death, Caspase, Bcl-2, BH3 interacting domain death agonist, Bcl-2-associated X protein

22

Eugenol and its related compounds are major active constituents of essential oils and have been extensively used as food flavoring agents with significant lipid peroxidation inhibition activity, highlighting the importance of understanding detailed molecular mechanisms behind their interactions with lipid bilayer. For this, we studied antioxidant activity of essential oils rich extract of Cinnamomum tamala leaves and molecular dynamics simulations of eugenol, isoeugenol, methyleugenol, acetyleugenol and eugenol oxide in POPC and PLPC lipid bilayers. All the compounds penetrated into bilayer however, isoeugenol showed highest affinity for the pure POPC and PLPC bilayers with lowest free energy profiles, formed more H-bonds with bilayer oxygen atoms and more pronounced changes in area per lipid and thickness of the bilayer, thus more efficient for scavenging radicals coming from outside as well as centrally located lipid peroxyl radicals. These molecular interactions rationalize the difference in inhibition activities of lipid peroxidation by eugenol and its related compounds.

Concepts: Oxygen, Antioxidant, Reactive oxygen species, Chemical bond, Lipid, Cinnamon, Lipid bilayer, Bay leaf

2

Aggregation of the protein α-Synuclein (αSyn) is of great interest due to its involvement in the pathology of Parkinson’s disease. However, under in vitro conditions αSyn is very soluble and kinetically stable for extended time periods. As a result, most αSyn aggregation assays rely on conditions that artificially induce or enhance aggregation, often by introducing rather non-native conditions. It has been shown that αSyn interacts with membranes and conditions have been identified in which membranes can promote as well as inhibit αSyn aggregation. It has also been shown that αSyn has the intrinsic capability to assemble lipid-protein-particles, in a similar way as apolipoproteins can form lipid-bilayer nanodiscs. Here we show that these αSyn-lipid particles (αSyn-LiPs) can also effectively induce, accelerate or inhibit αSyn aggregation, depending on the applied conditions. αSyn-LiPs therefore provide a general platform and additional tool, complementary to other setups, to study various aspects of αSyn amyloid fibril formation.

1

Lipids secreted from the meibomian glands form the outermost layer of the tear film and reduce its evaporation. Abnormal changes in the quantities or compositions of lipids present in meibomian gland secretions (meibum) are known to lead to dry eye disease, although the underlying mechanism is not yet well understood. The tree shrew is the non-primate mammal most closely related to humans. To assess the utility of the tree shrew as a model for the study of dry eye disease, we analyzed the lipid profile of tree shrew meibum using an untargeted ESI-MS and MS/MSall shotgun approach. The resulting lipidome shared many similarities with human meibum, while also displaying some interesting differences. For example, several classes of lipids, including wax esters, cholesteryl esters, diesters, and OAHFAs, had relatively longer chain lengths in tree shrew meibum. These increases in length may promote more effective reduction of tear evaporation in the tree shrew, which likely underlies the much longer blinking interval of this mammal. Our results suggest that the tree shrew could be an effective model for study of dry eye.

0

Simvastatin belongs to the statin family of cholesterol lowering drugs which act as competitive inhibitors of HMG-CoA reductase, the rate-determining enzyme in cholesterol biosynthesis pathway. Simvastatin is a semi-synthetic, highly lipophilic statin, and has several side effects. Since HMG-CoA reductase is localized in the endoplasmic reticulum, orally administered simvastatin needs to cross the cellular plasma membrane to be able to act on HMG-CoA reductase. With an overall goal of exploring the interaction of simvastatin with membranes, we examined the effect of simvastatin on the organization and dynamics in membranes of varying phase, in a depth-dependent manner. For this, we employed DPH and TMA-DPH, which represent fluorescent membrane probes localized at two different locations (depths) in the membrane. Analysis of fluorescence anisotropy and lifetime data of these depth-specific probes in membranes of varying phase (gel/fluid/liquid-ordered) showed that the maximum membrane disordering was observed in gel phase, while moderate effects were observed in liquid-ordered phase, with no significant change in membrane order in fluid phase membranes. We conclude that simvastatin induces change in membrane order in a depth-dependent and phase-specific manner. These results provide novel insight in the membrane interaction of simvastatin and could be crucial for understanding its pharmacological effect.

0

Bone diseases are notoriously difficult diseases to treat due to the comparatively low blood flows in bone tissue. Therefore, targeting delivery of drugs to bone may not only enhance the treatment efficacy, but also reduce the quantity of drug administered. In order to increase the distribution of paclitaxel (PTX) in bone, in this study, a series of novel dendritic aspartic acid derivatives were designed and synthesized as liposome ligands to deliver PTX to bone effectively. The liposomes were prepared by thin film hydration method and its particle size, zeta potential, encapsulation efficiency, release profile, stability, hemolysis were also characterized. All the aspartic acid-coated liposomes showed more than 60% binding rates to hydroxyapatite (HAP), especially the PTX-Asp8-Lip exhibited dramatic binding rates (> 97%) after 24 h. Moreover, the bone-targeting study in vivo indicated that all liposomes could improve the accumulation of PTX in bone, among which, the PTX-Asp8-Lip showed the best affinity due to the increase of aspartic acid residues exposed on the liposome surface. These results provided a novel and effective entry to the development of bone-targeting drugs.

0

Regarding free genistein small delivery to the central nervous system, physico-chemical parameters of dimiristoylphosphatidylcholine liposome-loaded genistein were investigated, as well as its in vitro activity against the DPPH radical and glioma cells. Data obtained by UV-visible spectroscopy, Fourier Transform Infrared Spectroscopy, Nuclear Magnetic Resonance, Differential Scanning Calorimetry and Dynamic Light Scattering were used to characterize the liposomal system with respect to motion restriction, hydration degree, trans-gauche isomerization and phase state. In vitro antitumoral effects were monitored through conting and viability assays. Genistein hydroxyl group and lipid hydrogen bonds may have important role in dimiristoylphosphatidylcholine phosphate and choline motion restriction. Genistein-induced choline restriction may be also related to a decrease in the group rotation rate. Genistein: dimiristoylphosphatidylcholine system showed higher molecular package at the acyl chains region compaired to empty liposomes, and it may be related to a decrease in gauche bonds quantity and system size. Lipid acyl chain length seems to influence different genistein effects on membranes, due to the presence of gauche conformers. Genistein: dimiristoylphosphatidylcholine liposome was more efficient as DPPH reducting system than the free-Gen. Liposomal system, at genistein 100 μM, was so efficient as the correspondent free-form genistein, probably showing higher stability to cross the blood-brain barrier. Genistein and the lipid did not show an additive activity against glioma cells. Antioxidant and anti-glioma genistein-loaded liposome potential may be related to the isoflavone location and its restriction effect in the lipid molecular motion. Anti-glioma activity may also be related to a decrease of system size and trans-gauche isomerization.

0

Lipid/surfactant miscibility was investigated in monolayers composed of binary mixtures of dipalmitoylphosphatidylglycerol (DPPG) and dihexadecyl dimethylammonium bromide (DHDAB). Langmuir monolayers formed from biomimetic DPPG/DHDAB mixtures based on the anionic:cationic lipid ratios observed in the bacterium Staphylococcus aureus (7:3 and 1:1) were examined alongside those of the pure amphiphiles and a surfactant rich 3:7 mixture. Using a combination of GIXD, TRXF and IRRAS, DPPG/DHDAB 1:1 monolayers were found to form a more stabilised condensed phase compared to pure DPPG, which was composed entirely of electrostatically neutral ion pairs, analogous to the so-called catanionic amphiphiles spontaneously formed by single-chain surfactants with opposing headgroup charges. Despite the lack of lateral charge repulsion the ion paired phase of DPPG/DHDAB exhibited slightly looser chain packing that was observed for DPPG indicating a significant steric effect on packing geometry caused by ion pair formation. Surprisingly, the 7:3 mixture of DPPG/DHDAB formed an completely condensed phase, with no isotherm transitions, in which the chain packing was significantly closer than was found for either DPPG or the totally ion paired monolayer. It is postulated that this mixture forms a distinct DPPG/DHDAB/DPPG ion triplet phase in which the overall negative charge is delocalised across the headgroups. Vesicles composed from the 7:3 mixture formed highly stable dispersions with an increased gel to liquid crystalline phase transition temperature with respect to its pure components. Increasing the proportion of DHDAB above 50 mol% led to demixing between the condensed ion paired phase and the more fluid surfactant, as was clearly observed in epifluorescence images taken of the surface films.

0

Surface pressure (π) - molecular area (A) isotherms of cholesterol were precisely measured to get insight into the orientation of molecules in Langmuir monolayers, which allowed to obtain detailed information on their phase behaviour. This was possible from the detailed analysis of the interfacial compressibility modulus versus surface pressure (Cs-1- π) plots (obtained from the experimental surface pressure, π - area, A isotherms) and films thickness measurements (applying Brewster angle microscope, BAM) complemented with polarization-modulation infrared reflection-absorption spectroscopy (PM-IRRAS). At first glance, the isotherm for cholesterol is characterized by the major slope change of surface pressure versus area per molecule. However, a more detailed analysis showed the presence of a discontinuity and slope change both upon the compression and expansion of the monolayer. This discontinuity is more accurately reflected in the Cs-1- π plot as a pseudo-plateau visible at π values between approximately 5 and 10 mN/m. This plateau was found to be temperature-dependent. Also, film thickness versus area plot (th-A) exhibits a pseudo-plateau in this region of surface pressures, in which the monolayer thickness increased gradually from 1.15 nm to 1.5 nm. Interestingly, although cholesterol has been intensively investigated in Langmuir monolayers, the existence of such a plateau have been overlooked previously. By linking experimental thickness values with theoretical molecular conformations, we have identified the presence of this plateau to the solid-solid (S-S') second-order transition. Using 2D analog of Clausius-Clapeyron equation, the thermodynamic functions (ΔH and ΔS) for this transition have been calculated. Based on monolayer experiments, the orientation of molecules in both solid phases was assumed to differ in the orientation of short alkyl chain attached to C17, which has additionally been confirmed with PM-IRRAS analysis.