摘要 :
The influence of monovalent salts (NaF, NaCl, NaBr, NaClO_4, KCl) on the properties of lipid bilayers composed of binary mixtures of zwitterionic DOPC (dioleoylphosphatidylcholine) and cationic DOTAP (dioleoyltrimethylammoniumprop...
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The influence of monovalent salts (NaF, NaCl, NaBr, NaClO_4, KCl) on the properties of lipid bilayers composed of binary mixtures of zwitterionic DOPC (dioleoylphosphatidylcholine) and cationic DOTAP (dioleoyltrimethylammoniumpropane) is experimentally measured and numerically simulated. Both approaches report a specific adsorption of the studied anions at the cationic bilayer. The adsorption is enhanced for higher content of DOTAP in DOPC/DOTAP mixtures and for larger anions (Br~- and ClO_4~-). The nonmonotonic dependence of the lipid headgroup mobility, determined using time-dependent fluorescence shifts of Laurdan located at the bilayer carbonyl level, on the content of cationic lipid is preserved in all examined salt solutions. Its maximum, however, is shifted towards higher DOTAP concentrations in the row: NaF < NaCl < NaBr. The same ordering of salts is found for the simulated area per lipid and the measured rigidification of pure DOTAP bilayers. Simulations reveal that Br~- strongly binds to the cationic headgroups of DOTAP neutralising the bilayer, which induces lateral inhomogeneities in the form of hydrophilic and hydrophobic patches at the membrane-water interface for pure DOTAP. In the equimolar DOPC/DOTAP mixture the neutralising effect of Br~- results in bending of the PC headgroups to a bilayer-parallel orientation. F~-, while attracted to the DOTAP bilayer, has an opposite effect to that of Br~-, i.e. it increases local mobility at the lipid carbonyl level. We attribute this effect to the disruption of the hydrogen-bonded structure of the molecules of lipids and water caused by the presence of the adsorbed F~-.
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Cyanidin and its O-glycosides have many important physiological functions in plants and beneficial effects on human health.Their biological activity is not entirely clear and depends on the structure of the molecule,in particular,...
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Cyanidin and its O-glycosides have many important physiological functions in plants and beneficial effects on human health.Their biological activity is not entirely clear and depends on the structure of the molecule,in particular,on the number and type of sugar substituents.Therefore,in this study the detailed structure-activity relationship(SARs)of the anthocyanins/anthocyanidins in relation to their interactions with lipid bilayer was determined.On the basis of their antioxidant activity and the changes induced by them in size and Zeta potential of lipid vesicles,and mobility and order of lipid acyl chains,the impact of the number and type of sugar substituents on the biological activity of the compounds was evaluated.The obtained results have shown,that 3-O-glycosylation changes the interaction of cyanidin with lipid bilayer entirely.The 3-O-glycosides containing a monosaccharide induces greater changes in physical properties of the lipid membrane than those containing disaccharides.The presence of additional sugar significantly reduces glycoside interaction with model lipid membrane.Furthermore,O-glycosylation alters the ability of cyanidin to scavenge free radicals.This alteration depends on the type of free radicals and the sensitivity of the method used for their determination.
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摘要 :
Cyanidin and its O-glycosides have many important physiological functions in plants and beneficial effects on human health. Their biological activity is not entirely clear and depends on the structure of the molecule, in particula...
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Cyanidin and its O-glycosides have many important physiological functions in plants and beneficial effects on human health. Their biological activity is not entirely clear and depends on the structure of the molecule, in particular, on the number and type of sugar substituents. Therefore, in this study the detailed structure-activity relationship (SARs) of the anthocyanins/anthocyanidins in relation to their interactions with lipid bilayer was determined. On the basis of their antioxidant activity and the changes induced by them in size and Zeta potential of lipid vesicles, and mobility and order of lipid acyl chains, the impact of the number and type of sugar substituents on the biological activity of the compounds was evaluated. The obtained results have shown, that 3-O-glycosylation changes the interaction of cyanidin with lipid bilayer entirely. The 3-O-glycosides containing a monosaccharide induces greater changes in physical properties of the lipid membrane than those containing disaccharides. The presence of additional sugar significantly reduces glycoside interaction with model lipid membrane. Furthermore, O-glycosylation alters the ability of cyanidin to scavenge free radicals. This alteration depends on the type of free radicals and the sensitivity of the method used for their determination.
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Fluidity of lipid membranes is known to play an important role in the functioning of living organisms.The fluorescent probe Laurdan embedded in a lipid membrane is typically used to assess the fluidity state of lipid bilayers by u...
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Fluidity of lipid membranes is known to play an important role in the functioning of living organisms.The fluorescent probe Laurdan embedded in a lipid membrane is typically used to assess the fluidity state of lipid bilayers by utilizing the sensitivity of Laurdan emission to the properties of its lipid environment.In particular,Laurdan fluorescence is sensitive to gel vs liquid-crystalline phases of lipids,which is demonstrated in different emission of the dye in these two phases.Still,the exact mechanism of the environment effects on Laurdan emission is not understood.Herein,we utilize dipalmitoylphosphatidylcholine(DPPC)and dioleoylphosphatidylcholine(DOPC)lipid bilayers,which at room temperature represent gel and liquid-crystalline phases,respectively.We simulate absorption and emission spectra of Laurdan in both DOPC and DPPC bilayers with quantum chemical and classical molecular dynamics methods.We demonstrate that Laurdan is incorporated in heterogeneous fashion in both DOPC and DPPC bilayers,and that its fluorescence depends on the details of this embedding.
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Fluidity of lipid membranes is known to play an important role in the functioning of living organisms. The fluorescent probe Laurdan embedded in a lipid membrane is typically used to assess the fluidity state of lipid bilayers by ...
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Fluidity of lipid membranes is known to play an important role in the functioning of living organisms. The fluorescent probe Laurdan embedded in a lipid membrane is typically used to assess the fluidity state of lipid bilayers by utilizing the sensitivity of Laurdan emission to the properties of its lipid environment. In particular, Laurdan fluorescence is sensitive to gel vs liquid–crystalline phases of lipids, which is demonstrated in different emission of the dye in these two phases. Still, the exact mechanism of the environment effects on Laurdan emission is not understood. Herein, we utilize dipalmitoylphosphatidylcholine (DPPC) and dioleoylphosphatidylcholine (DOPC) lipid bilayers, which at room temperature represent gel and liquid–crystalline phases, respectively. We simulate absorption and emission spectra of Laurdan in both DOPC and DPPC bilayers with quantum chemical and classical molecular dynamics methods. We demonstrate that Laurdan is incorporated in heterogeneous fashion in both DOPC and DPPC bilayers, and that its fluorescence depends on the details of this embedding.
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Although there exist a number of methods, such as NMR, X-ray, e.g., which explore the hydration of phospholipid bilayers, the solvent relaxation (SR) method has the advantage of simple instrumentation, easy data treatment and poss...
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Although there exist a number of methods, such as NMR, X-ray, e.g., which explore the hydration of phospholipid bilayers, the solvent relaxation (SR) method has the advantage of simple instrumentation, easy data treatment and possibility of measuring fully hydrated samples. The main information gained from SR by the analysis of recorded “time-resolved emission spectra” (TRES) is micro-viscosity and micro-polarity of the dye microenvironment. Based on these parameters, one can draw conclusions about water structure in the bilayer. In this review, we focus on physical background of this method, on all the procedures that are needed in order to obtain relevant parameters, and on the requirements on the fluorescence dyes. Furthermore, a few recent applications (the effect of curvature, binding of antibacterial peptides and phase transition) illustrating the versatility of this method are mentioned. Moreover, limitations and potential problems are discussed.
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The environment-sensitive fluorescent probes provide excellent tools for studying membranes in their native state. We have modified the BODIPY-based fluorescent molecular rotor by increasing the number of alkyl moieties from one t...
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The environment-sensitive fluorescent probes provide excellent tools for studying membranes in their native state. We have modified the BODIPY-based fluorescent molecular rotor by increasing the number of alkyl moieties from one to two or three to achieve a more defined and deeper positioning of the probe in membranes. Detailed characterisation of fluorescence properties and localisation/orientation of probes was performed using a variety of fluorescence techniques and model membranes composed of different lipids. As expected, additional alkyls attached to the fluorophore moiety led to a deeper and more defined localisation of the probe in the lipid bilayer. The results strongly indicate that fluorescence properties of such probes are influenced not only by lipid packing but also by the orientation of the probe in membranes. The orientation of rotors studied herein was significantly altered by changes in the lipid composition of membranes. Our observations demonstrate the limits of BODIPY-based molecular rotors as environmental sensors in cellular membranes with complex lipid composition. The results presented herein also underline the importance of the detailed characterisation of fluorescent membrane dyes and provide a guide for future testing.
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We claim that (1) cholesterol protects bilayers from disruption caused by lipid oxidation by sequestering conical shaped oxidized lipid species such as 1-palmitoyl-2-azelaoyl-sn-glycero-3-phosphocholine (PZPC) away from phospholip...
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We claim that (1) cholesterol protects bilayers from disruption caused by lipid oxidation by sequestering conical shaped oxidized lipid species such as 1-palmitoyl-2-azelaoyl-sn-glycero-3-phosphocholine (PZPC) away from phospholipid, because cholesterol and the oxidized lipid have complementary shapes and (2) mixtures of cholesterol and oxidized lipids can self-assemble into bilayers much like lysolipid- cholesterol mixtures. The evidence for bilayer protection comes from molecular dynamics (MD) simulations and dynamic light scattering (DLS) measurements. Unimodal size distributions of extruded vesicles (LUVETs) made up of a mixture of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and PZPC containing high amounts of PZPC are only obtained when cholesterol is present in high concentrations. In simulations, bilayers containing high amounts of PZPC become porous, unless cholesterol is also present. The protective effect of cholesterol on oxidized lipids has been observed previously using electron paramagnetic resonance (EPR) and electron microscopy imaging of vesicles. The evidence for the pairing of cholesterol and PZPC comes mainly from correlated 2-D density and thickness plots from simulations, which show that these two molecules co-localize in bilayers. Further evidence that the two molecules can cohabitate comes from self-assembly simulations, where we show that cholesteroloxidized lipid mixtures can form lamellar phases at specific concentrations, reminiscent of lysolipid- cholesterol mixtures. The additivity of the packing parameters of cholesterol and PZPC explains their cohabitation in a planar bilayer. Oxidized lipids are ubiquitously present in significant amounts in highand low-density lipoprotein (HDL and LDL) particles, diseased tissues, and in model phospholipid mixtures containing polyunsaturated lipids. Therefore, our hypothesis has important consequences for cellular cholesterol trafficking; diseases related to oxidized lipids, and to biophysical studies of phase behaviour of cholesterol-containing phospholipid mixtures.
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Positioning of peptides with respect to membranes is an important parameter for biological and biophysical studies using model systems. Our experiments using five different membrane peptides suggest that the time-dependent fluores...
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Positioning of peptides with respect to membranes is an important parameter for biological and biophysical studies using model systems. Our experiments using five different membrane peptides suggest that the time-dependent fluorescence shift (TDFS) of Laurdan can help when distinguishing between peripheral and integral membrane binding and can be a useful, novel tool for studying the impact of transmembrane peptides (TMP) on membrane organization under near-physiological conditions. This article focuses on LAH_4, a model α-helical peptide with high antimicrobial and nucleic acid transfection efficiencies. The predominantly helical peptide has been shown to orient in supported model membranes parallel to the membrane surface at acidic and, in a transmembrane manner, at basic pH. Here we investigate its interaction with fully hydrated large unilamellar vesicles (LUVs) by TDFS and fluorescence correlation spectroscopy (FCS). TDFS shows that at acidic pH LAH_4 does not influence the glycerol region while at basic pH it makes acyl groups at the glycerol level of the membrane less mobile. TDFS experiments with antimicrobial peptides alamethicin and magainin 2, which are known to assume transmembrane and peripheral orientations, respectively, prove that changes in acyl group mobility at the glycerol level correlate with the orientation of membrane-associated peptide molecules. Analogous experiments with the TMPs LW21 and LAT show similar effects on the mobility of those acyl groups as alamethicin and LAH_4 at basic pH. FCS, on the same neutral lipid bilayer vesicles, shows that the peripheral binding mode of LAH_4 is more efficient in bilayer permeation than the transmembrane mode. In both cases, the addition of LAH_4 does not lead to vesicle disintegration. The influence of negatively charged lipids on the bilayer permeation is also addressed.
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By means of molecular dynamics simulations with an all-atom force field, we investigated the affinities of alkali cations and halide anions for the dioleoylphosphatidylcholine lipid membrane in aqueous salt solutions. In addition,...
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By means of molecular dynamics simulations with an all-atom force field, we investigated the affinities of alkali cations and halide anions for the dioleoylphosphatidylcholine lipid membrane in aqueous salt solutions. In addition, changes in phospholipid lateral diffusion and in headgroup mobility upon adding NaCI were observed using fluorescence spectroscopy. The simulations revealed that sodium is attracted to the headgroup region with its concentration being maximal in the vicinity of the phosphate groups. Potassium and cesium, however, do not preferentially adsorb to the membrane. Similarly, halide anions do not exhibit a strong affinity for the lipid headgroups but merely compensate for the positive charge of the sodium countercations. Nevertheless, larger halides such as bromide and iodide penetrate deeper into the headgroup region toward the boundary with the hydrophobic alkyl chain, this effect being likely underestimated within the present nonpolarizable force field. Addition of alkali halide salts modifies physical properties of the bilayer including the electronic density profiles, the electrostatic potential, and the area per lipid headgroup.
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