Influence of organotin compounds on phosphatidylserine membranes

Organotin compounds are widely distributed toxicants. They are membrane‐active molecules with broad biological toxicity. We have studied the interaction of tributyltin and triphenyltin with phosphatidylserine model membranes using differential scanning calorimetry, infrared spectroscopy and X‐ray diffraction techniques. Organotin compounds produced a broadening of the gel to the liquid‐crystalline phase transition of the phospholipid and a shifting of the phase transition temperature to lower values. Infrared spectroscopy experiments showed that tributyltin exerted a fluidizing effect on the apolar part of the bilayer, and that both tributyl‐ and triphenyltin interact with the interfacial region of the bilayer, making the carbonyl groups less accessible to water. As seen by X‐ray diffraction experiments, organotin compounds were unable to change the bilayer macroscopic organization of the phospholipid, but they were able to reduce the long‐range order of the multibilayer system and to disorder the packing of the phospholipid molecules. The observed interaction between organotin compounds and phosphatidylserine membranes promotes physical perturbations that could affect membrane function and may mediate some of their toxic effects. Copyright © 2004 John Wiley & Sons, Ltd.     

Combined Monte Carlo and molecular dynamics simulation of hydrated 18:0 sphingomyelin-cholesterol lipid bilayers

We have carried out atomic level molecular dynamics and Monte Carlo simulations of hydrated 18:0 sphingomyelin (SM)-cholesterol (CHOL) bilayers at temperatures of 20 and 50 degrees C. The simulated systems each contained 266 SM, 122 CHOL, and 11861 water molecules. Each simulation was run for 10 ns under semi-isotropic pressure boundary conditions. The particle-mesh Ewald method was used for long-range electrostatic interactions. Properties of the systems were calculated over the final 3 ns. We compare the properties of 20 and 50 degrees C bilayer systems with each other, with experimental data, and with experimental and simulated properties of pure SM bilayers and dipalmitoyl phospatidyl choline (DPPC)-CHOL bilayers. The simulations reveal an overall similarity of both systems, despite the 30 degrees C temperature difference which brackets the pure SM main phase transition. The area per molecule, lipid chain order parameter profiles, atom distributions, and electron density profiles are all very similar for the two simulated systems. Consistent with simulations from our lab and others, we find strong intramolecular hydrogen bonding in SM molecules between the phosphate ester oxygen and the hydroxyl hydrogen atoms. We also find that cholesterol hydroxyl groups tend to form hydrogen bonds primarily with SM carbonyl, methyl, and amide moieties and to a lesser extent methyl and hydroxyl oxygens.     

Density Functional Theory Study of the Interaction between Guanine and Catechin

The interacting patterns and mechanism of the catechin and guanine have been investigated with the density functional theory B3LYP method by 6‐31G* basis set. Fourteen stable structures for the catechin‐guanine complexes have been found which form two hydrogen bonds at least. The results indicate that the complexes are mainly stabilized by the hydrogen bonding interactions. At the same time, the number and strength of hydrogen bond play a co‐determinant parts in the stability of the complexes which can form two or more hydrogen bonds. Theories of atoms in molecules (AIM) and natural bond orbital (NBO) have been adopted to investigate the hydrogen bonds involved in all systems. The interaction energies of all complexes have been corrected for basis set superposition error (BSSE), ranging from ?38.86 to ?14.56 kJ/mol. The results showed that the hydrogen bonding contributes to the interaction energies dominantly. The corresponding bonds stretching motions in all complexes are red‐shifted relative to that of the monomer, which is in agreement with experimental results.     

Raman study of a liquid crystalline gel consisting of photochromic 4‐methyl‐N‐(4‐n‐heptyloxysalicylidene)aniline and a gelling agent (R,R′)‐1,2‐bis(dodecanoylamino)cyclohexane

A liquid crystalline physical gel has been prepared from the mixture of a nematic liquid crystal and a low molecular mass gelling agent containing a hydrogen‐bonding moiety. The newly synthesized liquid crystalline compound exhibited photochromism in the crystalline solid phase. Although photochromism was not observed in the nematic gel state of the mixture, the lifetime of photochromism in the solid phase became longer, compared with that of a single liquid crystalline compound. Some Raman bands of the mixture showed a marked change in both intensity and frequency through the phase transitions. These bands have been assigned to the vibrational modes related to the core part of molecule.     

Density Functional Theory Study on Interaction between Catechin and Thymine

The interacting patterns and mechanism of the catechin and thymine have been investigated with the density functional theory Becke's three-parameter nonlocal exchange functional and the Lee, Yang, and Parr nonlocal correlation functional (B3LYP) method by 6-31+G*basis set. Thirteen stable structures for the catechin-thymine complexes have been found which form two hydrogen bonds at least. The vibrational frequencies are also studied at the same level to analyze these complexes. The results indicated that catechin interactedwith thymine by three different hydrogen bonds as N-H…O、C-H…O、O-H…O and the complexes are mainly stabilized by the hydrogen bonding interactions. Theories of atoms in molecules and natural bond orbital have been adopted to investigate the hydrogen bondsinvolved in all systems. The interaction energies of all complexes have been corrected for basis set superposition error, which are from -18.15 kJ/mol to -32.99 kJ/mol. The results showed that the hydrogen bonding contribute to the interaction energies dominantly. The corresponding bonds stretching motions in all complexes are red-shifted relative to that of the monomer, which is in agreement with experimental results.     

Complexation of cationic polyelectrolyte with anionic phospholipid vesicles: Concentration, molecular weight and salt effects

The influence of cationic poly(diallyldimethylammonium chloride) on the morphology and phase behavior of anionic phospholipid vesicles was investigated using differential scanning calorimetry, fluorescent microscopy and light scattering technique. A wide range of polymer concentration has been examined for the first time. The polycation can bind electrostatically to the vesicles to compensate, neutralize and reverse the vesicular charge, depending on the molar ratio of cationic to anionic group R. For R<1, charge compensation weakened the electrostatic repulsion between the lipid molecules, leading to formation of polymer-modified vesicles, each with an increased number of bilayers. The bilayer exhibits a rising main phase transition temperature from a gel to liquid crystalline state. This behavior persisted until R≈1 around the neutralization condition, where the complexes became largest and precipitate. With R>1, charge reversal took place, the complex size reduced. Interestingly, the main phase transition temperature was found for the first time to shift back towards the original value in the absence of polymer for large enough R. Although the thermal behavior was nearly independent of the polymer molecular weight, the complex morphology could be different.     

Chain-melting phase transition and short-range molecular interactions in phospholipid foam bilayers

Occurrence of two-dimensional chain melting phase transition in foam bilayers was established for the first time. Microscopic horizontal foam bilayers [Newton black films (NBF)] were investigated by the microinterferometric method of Scheludko-Exerowa. The foam bilayers were formed from water-ethanol solutions of dimyristoylphosphatidylcholine (DMPC) and dipalmitoylphosphatidylcholine (DPPC) and egg phosphatidylcholine (Egg PC) and samples of amniotic fluid (AF) at different temperatures. The influence of temperature on the foam bilayer thickness h(w) and on the critical concentration Cc for formation of foam bilayer was studied. It was shown that in the range of the main phase transition the temperature dependence of h(w) and C(c) changed specifically in the case of DMPC and DPPC foam bilayers. The thickness of the foam bilayers increased with decreasing temperature in the range of the main phase transition due to the melting of hydrocarbon tails of phospholipid molecules. These changes took place at the temperatures of the bulk chain-melting phase transitions, as determined by differential scanning calorimetry (DSC) for both aqueous, and water/ethanol DMPC, DPPC, and DPPC dispersions. An effect of the 'disperse medium' on h(w) was found for foam bilayers from DPPC. The results that foam bilayers could have different thickness at different temperatures disproved the current concept that NBF acquired constant thickness at concentrations higher than C(el,cr). The data for Cc were analysed on the basis of the hole-nucleation theory of bilayer stability of Kashchiev and Exerowa. This theory considered the amphiphile bilayer as a two-dimensional ordered system with short-range molecular interactions between the first neighbour molecules (as in a crystal). The short-range molecular interactions were presented by the parameter binding energy Q of an amphiphile molecule in the bilayer. The binding energy Q of two neighbouring phospholipids was calculated for the gel (30-60 kT) and liquid crystalline state (16-18 kT) of the bilayers from DMPC, DPPC, Egg PC, AF. Concentration/temperature phase diagram of DPPC foam bilayers that defined regions of gaseous (ruptured), gel and liquid crystalline foam bilayers were drawn. The values of Q obtained for various samples were very close and vary from 5.3 x 10(-20) to 9.4 x 10(-20) (approx. 13-22 kT) which indicated that in all cases the foam bilayers were in liquid-crystalline state. This is an important result since the parameter studied-threshold concentration (threshold dilution) is crucial for a very successful assessment of the risk for respiratory distress syndrome (RDS) in newborns and could be employed in medicine for assessment of other respiratory disturbances. It is to be expected that foam bilayers from phospholipids could be used as a model for investigation of short-range forces in biological structures, of interaction between membranes, etc.     

Molecular dynamics investigation of dynamical properties of phosphatidylethanolamine lipid bilayers

We describe the dynamic behavior of a 1-stearoyl-2-oleoyl-phosphatidylethanolamine (SOPE) bilayer from a 20 ns molecular dynamics simulation. The dynamics of individual molecules are characterized in terms of (2)H spin-lattice relaxation rates, nuclear overhauser enhancement spectroscopy (NOESY) cross-relaxation rates, and lateral diffusion coefficients. Additionally, we describe the dynamics of hydrogen bonding through an analysis of hydrogen bond lifetimes and the time evolution of clusters of hydrogen bonded lipids. The simulated trajectory is shown to be consistent with experimental measures of internal, intermolecular, and diffusive motion. Consistent with our analysis of SOPE structure in the companion paper, we see hydrogen bonding dominating the dynamics of the interface region. Comparison of (2)H T(1) relaxation rates for chain methylene segments in phosphatidylcholine and phosphatidylethanolamine bilayers indicates that slower motion resulting from hydrogen bonding extends at least three carbons into the hydrophobic core. NOESY cross-relaxation rates compare well with experimental values, indicating the observed hydrogen bonding dynamics are realistic. Calculated lateral diffusion rates (4 +/ -1 x 10(-8) cm(2)s) are comparable, though somewhat lower than, those determined by pulsed field gradient NMR methods.     

Interaction of zervamicin IIB with lipid bilayers. Molecular dynamics study

In this work we have studied the interaction of zervamicin IIB (ZrvIIB) with the model membranes of eukaryotes and prokaryotes using all-atom molecular dynamics. In all our simulations zervamicin molecule interacted only with lipid headgroups but did not penetrate the hydrophobic core of the bilayers. During the interaction with the prokaryotic membrane zervamicin placed by its N-termini towards the lipids and rotated at an angle of 40° relatively to the bilayer surface. In the case of eukaryotic membrane zervamicin stayed in the water and located parallel to the membrane surface. We compared hydrogen bonds between peptide and lipids and concluded that interactions of ZrvIIB with prokaryotic membrane are stronger than those with eukaryotic one. Also it was shown that two zervamicin molecules formed dimer and penetrated deeper in the area of lipid headgroups.     

Effects of newcastle disease virus glycoproteins on the structural and thermal behaviour of 1,2-dihexadecyl-sn-glycero-3-phosphatidylcholine lipid membranes under osmotic stress conditions

The interaction of hem agglutininneuraminidase (HN) and fusion (F) glycoproteins with swollen vesicles of 1,2-dihexadecyl-sn-glycero-3-phosphatidylcholine (DHPC) was investigated under transition from gel to fluid phase. X-ray studies of the structure of lipid/HN-F mixtures in normal and swollen vesicles have shown that the lamellar bilayer structure predominate in the gel and liquid crystalline phases. A swollen lipid phase, in which the mean repeat distance of lipid bilayers is larger than in the other phases was found. The nature of this phase is similar to the anomalous bilayer swelling reported in literature. The presence of HN and F in the vesicles led to the coexistence of structures with low and high lamellar order, showing larger repeat distance in comparison with the pure lipid. This finding was attributed to the increase in the lipid bilayer thickness due to the HN-F included in the free water layer. The thermal behaviour of the system was not affected by the vesicle swelling. The data showed the existence of gel and liquid crystalline lamellar phases and changes in lipid/HN-F specific heats, mainly due to the concentration effect of the HN-F and its location in the free water layer.     

Synthesis of a New Self-Assembly Liquid Crystalline Polymer Through Intermolecular Hydrogen Bonding

A new side chain liquid crystalline polymer with biphenyl mesogenic group has been prepared. This polymer forms a bilayer smectic A phase through intermolecular hydrogen bonding according to the result of X-ray diffraction. Its phase transition was studied lining DSC and polarized optical microscopy. Infrared spectroscopic measurements show that cyclic dimeric hydrogen bonds of carboxylic acids are embedded in the bilayer.     

Determination of the hydrogen-bonding induced local viscosity enhancement in room temperature ionic liquids via femtosecond time-resolved depleted spontaneous emission

The fluorescence depletion dynamics of Rhodamine 700 (R-700) molecules in room temperature ionic liquids (RTILs) 1-ethyl-3-methylimidazolium tetrafluoroborate ([emim][BF(4)]) and 1-hydroxyethyl-3-methylimidazolium tetrafluoroborate ([HOemim][BF(4)]) were investigated to determine the local viscosity of the microenvironment surrounding the fluorescent molecules, which is induced by strong hydrogen bonding interaction between cationic and anionic components in RTILs. The solvation and rotation dynamics of R-700 molecules in RTILs show slower time constants relative to that in conventional protic solvents with the same bulk viscosity, indicating that the probe molecule is facing a more viscous microenvironment in RTILs than in conventional solvents because of the strong hydrogen bonding interaction between cationic and anionic components. In addition, this effect is more pronounced in hydroxyl-functionalized ionic liquid than in the regular RTIL due to the presence of a hydroxyl group as a strong hydrogen bonding donor. The hydrogen-bonding-induced local viscosity enhancement effect related to the heterogeneity character of RTILs is confirmed by the nonexponential rotational relaxation of R-700 determined by time-correlated single photon counting (TCSPC). The geometry of hydrogen bonding complexes with different components and sizes are further optimized by density functional theory methods to show the possible hydrogen-bond networks. A model of the hydrogen-bonding network in RTILs is further proposed to interpret the observed specific solvation and local viscosity enhancement effect in RTILs, where most of the fluoroprobes exist as the free nonbonding species in the RTIL solutions and are surrounded by the hydrogen-bonding network formed by the strong hydrogen-bonding between the cationic and anionic components in RTIL. The optimized geometry of hydrogen bonding complexes with different components and sizes by density functional theory methods confirms the local viscosity enhancement effect deduced from fluorescence depletion and TCSPC experiments. The calculated interaction energies reveal the existence of the stronger hydrogen bonding network in RTILs (especially in hydroxyl-functionalized ionic liquid) than that in conventional protic solvent, which leads to the enhancement effect of local microviscosity, and therefore leads to the slow solvation and rotation dynamics of probe molecules observed in RTILs.     

α-生育酚在模型生物膜中的分子动力学模拟

用分子动力学方法模拟了280, 310和350 K下α-生育酚在二豆蔻酰磷脂酰胆碱、二豆蔻酰磷脂酰乙醇胺、二硬脂酰磷脂酰胆碱和二硬脂酰磷脂酰乙醇胺双层膜中的性质, 包括了空间位置、氢键、取向和动力学性质, 取得了如下的结论. 第一, 生育酚头部的羟基一般位于脂双层亲疏水界面的下方, 升高温度将促进羟基向膜双层的中心移动, 在350 K时观察到了在上下两个单层间的翻转. 第二, 生育酚主要与磷脂的酯基形成氢键, 几乎不与磷脂酰乙醇胺的氨基形成氢键; 比较生育酚与磷脂酰胆碱和乙醇胺形成的氢键后发现, 后者更稳定. 第三, 生育酚的头部在膜中取向多变, 与膜的法线夹角不固定, 尾部的构象也很复杂. 第四, 在温度较低时, 生育酚的侧向扩散系数与磷脂的相当, 但在350 K时其扩散速度明显加快; 在垂直方向生育酚的扩散速度很慢.     

Prodan fluorescence detects the bilayer packing of asymmetric phospholipids

The bilayer phase behavior of asymmetric phospholipids, palmitoylstearoylphosphatidylcholine (PSPC) and stearoylpalmitoylphosphatidylcholine (SPPC), with different vesicle sizes (large multilamellar vesicle (LMV) and giant multilamellar vesicle (GMV)) was investigated by fluorescence spectroscopy using a polarity-sensitive fluorescent probe Prodan under high pressure. The results were compared with those of a symmetric phospholipid, diheptadecanoyl PC (C17PC). The difference in phase transitions of the PSPC and SPPC bilayers and in thermodynamic quantities of the transitions was hardly observed between LMV and GMV as the case of the C17PC bilayer. On the other hand, the Prodan fluorescence showed clear differences between LMV and GMV of the asymmetric PC bilayers. From the second derivative of Prodan fluorescence spectra, the three dimensional image plots in which we can clearly see the location of Prodan in the bilayer membrane as blue valleys were constructed for LMV and GMV under high pressure. We revealed from the plots that the bilayer packing is significantly dependent on not only the vesicle size but also the acyl-chain asymmetry of PC molecule in addition to the phase states. It was found that the packing of the gel phases of the asymmetric PC bilayers is weaker than that of the symmetric PC bilayer, and the size of vesicle affects the packing of the interdigitated gel phase the most markedly among three gel phases. This study suggests that the Prodan molecules can detect the effect of vesicle size on the phase states for the asymmetric PC bilayers, and they become a useful indicator for various membrane properties, especially bilayer interdigitation.     

The antimalarial agent halofantrine perturbs phosphatidylcholine and phosphatidylethanolamine bilayers: a differential scanning calorimetric study.

The interaction of halofantrine with phosphatidylcholine and phosphatidylethanolamine bilayers has been investigated by differential scanning calorimetry. Halofantrine caused a broadening of the gel to liquid crystalline phase transition endotherm of the phosphatidylcholines. A decrease in the transition temperature Tm and enthalpy (delta H) of transition was also observed. This varied with the chain length of the phospholipid and was more pronounced with short chain members. Halofantrine-induced changes to the thermotropic characteristics of dipalmitoylphosphatidylcholine (DPPC)/cholesterol bilayers suggested that the penetration of halofantrine into the bilayer was diminished in the presence of cholesterol. A more complex calorimetric profile was observed in the interaction of halofantrine with phosphatidylethanolamines and the results suggested that halofantrine did not disrupt the cooperativity of the phosphatidylethanolamine bilayers to the same extent as that observed with the phosphatidylcholines. Halofantrine caused significant perturbation of phospholipids and this property might have an important bearing on its pharmacodynamic effects.     

Monte Carlo study of lipid membranes: Simulation of diparmitoylphosphatidylcholine bilayers in gel and liquid-crystalline phases

The statistical properties of the bilayer membranes of diparmitoylphosphatidylcholine (DPPC) in the gel and liquid-crystal phases were studied by Monte Carlo (MC) simulation using potential functions of the Lennard-Jones, the simple Coulomb, and the bond torsion. The simulation was undertaken on a two-dimensional periodic condition imposed on the bilayer model consisting of faithfully described molecules. The structure and ordering of the model bilayers accorded well with experiments, and the segment order parameters were in agreement with those of the nuclear magnetic resonance (NMR) experiments. The two kinds of lipid chains of DPPC do not equivalently behave in the bilayers, and chain 2 has lower ordering than chain 1. The order parameters of the first eight segments of chain 2 in the liquid-crystal model are particularly small and are roughly constant. From electron density analysis, it has been observed that the liquid-crystal bilayer has about one excess water molecule per one lipid molecule in comparison with the gel bilayer. The energy difference between the two bilayer models, taking account of the water contribution, is consistent with the latent heat of the phase transition. © 1995 by John Wiley & Sons, Inc.     

Coacervation of poly-electrolytes in the presence of lipid bilayers: mutual alteration of structure and morphology

Many intrinsically disordered peptides have been shown to undergo liquid–liquid phase separation and form complex coacervates, which play various regulatory roles in the cell. Recent experimental studies found that such phase separation processes may also occur at the lipid membrane surface and help organize biomolecules during signaling events; in some cases, phase separation of proteins at the membrane surface was also observed to lead to significant remodeling of the membrane morphology. The molecular mechanisms that govern the interactions between complex coacervates and lipid membranes and the impacts of such interactions on their structure and morphology, however, remain unclear. Here we study the coacervation of poly-glutamate (E₃₀) and poly-lysine (K₃₀) in the presence of lipid bilayers of different compositions. We carry out explicit-solvent coarse-grained molecular dynamics simulations by using the MARTINI (v3.0) force-field. We find that more than 20% anionic lipids are required for the coacervate to form stable contact with the bilayer. Upon wetting, the coacervate induces negative curvature to the bilayer and facilitates local lipid demixing, without any peptide insertion. The magnitude of negative curvature, extent of lipid demixing, and asphericity of the coacervate increase with the concentration of anionic lipids. Overall, we observe a decrease in the number of contacts among the polyelectrolytes as the droplet spreads over the bilayer. Therefore, unlike previous suggestions, interactions among polyelectrolytes do not constitute a driving force for the membrane bending upon wetting by the coacervate. Rather, analysis of interaction energy components suggests that bending of the membrane is favored by enhanced interactions between polyelectrolytes with lipids as well as with counterions. Kinetic studies reveal that, at the studied polyelectrolyte concentrations, the coacervate formation precedes bilayer wetting.

Intrinsically disordered polyelectrolytes undergoing liquid–liquid phase separation to form complex coacervates on a membrane, which profoundly alters the membrane morphology.     

Unusual fluorescence spectral response of 1-(4-N,N-dimethylaminophenylethynyl)pyrene towards the thermotropic phase change in lipid bilayer membranes

The applicability of 1-(4-N,N-dimethylaminophenylethynyl)pyrene (DMAPEPy), a pyrene derivative showing intramolecular charge transfer, as a prospective probe for lipid bilayer membranes has been evaluated. High sensitivity of DMAPEPy to solvent polarity and viscosity makes it to act both as a polarity-sensitive probe and as a fluorescence anisotropy probe. The molecule shows high partition efficiency towards bilayer membranes in both solid gel as well as in the liquid crystalline phases. The emission spectrum, quenching experiment and lifetime data suggest bimodal distribution of DMAPEPy in the bilayer. Using the solvent polarity scales the polarity parameters of the two locations in lipid bilayer have been estimated. In the bilayer environment it exhibits remarkable spectral changes with temperature. The thermotropic phase change of the bilayer is sensitively monitored by fluorescence intensity as well as fluorescence anisotropy parameters. DMAPEPy is also capable of sensing the changes induced by membrane modifiers like cholesterol.     

Self-assembled diols: synthesis, structure and dielectric studies

In single-, double-, and triple-chain amphiphilic diols the CONH group was replaced by CON(CH₃) in order to reduce the number of proton donor groups available for intermolecular hydrogen bonding. The resulting three new liquid crystalline diols were studied by DSC, X-ray and dielectric measurements, and show the mesophases SmA, Col_H2 or Cub_I2, depending on the number of decyloxy groups in the hydrophobic part of the molecule. The process of self-assembly to different liquid crystalline phases is well seen in the dielectric spectrum and details of this process are discussed together with results from the X-ray measurements. All the compounds show a high frequency dielectric absorption caused by the dynamics of the network of hydrogen bonds. An additional low frequency process related to the internal dynamics of the columns is seen only in the columnar phase.