Phase diagram of a ternary mixture of cholesterol and saturated and unsaturated lipids calculated from a microscopic model

We employ a molecular model to study a ternary mixture of saturated lipid, with tails of 16 carbons, a monounsaturated lipid with tails of 18 carbons, and cholesterol. The model, solved within mean-field theory, produces several forms of phase diagrams depending upon the relative strengths of interactions, but only one that shows the coexistence of two liquid phases observed in experiment. The lipids in the phase rich in cholesterol are more ordered than those in the other. The binary cholesterol, saturated lipid system also exhibits liquid, liquid coexistence.     

Combined effects of headgroup charge and tail unsaturation of lipids on lateral organization and diffusion of lipids in model biomembranes

Lateral organization and dynamics of lipids in plasma membranes are crucial for several cellular processes such as signal transduction across the membrane and still remain elusive.In this paper,using coarse-grained molecular dynamics simulation,we theoretically study the combined effects of headgroup charge and tail unsaturation of lipids on the lateral organization and diffusion of lipids in ternary lipid bilayers.In neutral ternary lipid bilayers composed of saturated lipids,unsaturated lipids,and cholesterols,under the conditions of given temperature and components,the main factor for the phase separation is the unsaturation of unsaturated lipids and the bilayers can be separated into liquid-ordered domains enriched in saturated lipids and cholesterols and liquid-disordered domains enriched in unsaturated lipids.Once the headgroup charge is introduced,the electrostatic repulsion between the negatively charged lipid headgroups will increase the distance between the charged lipids.We find that the lateral organization and diffusion of the lipids in the(partially) charged ternary lipid bilayers are determined by the competition between the headgroup charge and the unsaturation of the unsaturated lipids.In the bilayers containing unsaturated lipids with lower unsaturation,the headgroup charge plays a crucial role in the lateral organization and diffusion of lipids.The headgroup charge may make the lipid domains unstable and even can suppress phase separation of the lipids in some systems.However,in the bilayers containing highly unsaturated lipids,the lateral organization and diffusion of lipids are mainly dominated by the unsaturation of the unsaturated lipids.This work may provide some theoretical insights into understanding the formation of nanosized domains and lateral diffusion of lipids in plasma membranes.     

The mechanism of surface heterodiffusion at elevated temperatures

Molecular dynamics simulations employing the Lennard-Jones potential have been performed on Kr/Ar(111) to investigate the nature of high-temperature surface heterodiffusion. These suggest that high activation energies and preexponential factors observed experimentally at temperatures above approximately 0.70 T_m arise from adatom-vacancy pair formation, which sharply increases the number of mobile species. Evidence is also obtained that at intermediate temperatures (0.45 T_m < T < 0.66 T_m), Arrhenius curves mass transfer diffusivity can depend on both coverage and adsorbate interactions. For adsorbates which exhibit islanding, low coverage diffusion is characterized by an activation energy equal to the enthalpy of migration, whereas at moderate coverage the activation energy contains an additional term due to the enthalpy of formation of mobile adatoms from immobile islands.     

Relations between intergranular diffusion and structure: A molecular dynamics study

The high temperature (T > 0.5T_m) structure of the previously studied fcc (310)[001] Σ = 5 grain boundary is reinvestigated in order to determine the nature of the diffusion mechanism. The obtained results confirm our earlier conclusion that the grain boundary remains crystalline, but highly disordered, up to the melting point. In addition, we explored the diffusion mechanisms in the fcc (210)[001] Σ = 5 grain boundary. As expected, diffusion occurs mainly by the vacancy migration. The jump frequencies determined by the molecular dynamics simulation have been used to evaluate the tracer correlation factor and the anisotropy of the intergranular diffusion coefficient through a random walk model simulation of the vacancy migration.     

活性浴中非活性棒的扩散动力学模拟研究：非单调尺寸依赖和反常平动-转动耦合

本文采用Langevin动力学模拟二维刚性棒状示踪粒子在活性浴中的扩散动力学,主要关注示踪粒子平动(转动)扩散系数随其棒长和背景粒子的活性强度如何变化. 本文发现示踪粒子在小时间尺度显示出超扩散行为,并在大时间尺度下恢复到正常扩散,同时平动扩散系数和转动扩散系数均随背景粒子的活性强度增加单调增加,但呈现出与棒长的非单调依赖. 在研究棒的平动-转动耦合时发现这种平衡系统中不存在反直觉现象,即棒在一定参数下会表现出负的平动-转动耦合,表明示踪粒子在平行于棒方向上的扩散比在垂直方向上更慢. 这种异常(扩散)行为随背景粒子的活性强度增加具有重入行为,表明背景粒子的活性导致了两种扩散行为存在竞争关系的效应.     

氢及其同位素在聚苯乙烯与Cu界面的扩散

为了探索气体在固体表面高分子链中的扩散,使用分子动力学（MD）的方法,对H2,D2,T2在聚苯乙烯与金属铜（PS-Cu）界面的扩散进行了计算模拟,通过所得到气体的均方位移计算了气体在不同金属表面与聚苯乙烯界面中的扩散系数。结果显示:气体在界面的扩散系数比在聚苯乙烯本体中的扩散系数小,气体在PS-Cu(110)界面的扩散系数最大,在PS-Cu(111)界面的扩散系数最小。计算和分析了PS与金属表面的相互作用,发现其相互作用能越大,气体在此界面的扩散系数越小。同时,金属表面的晶面密度对气体在界面中的扩散也有一定的影响。     

Transport of noble gases in poly(methyl acrylate)

The permeability, diffusivity, and solubility of He, Ne, Ar, and Kr were determined in poly(methyl acrylate) (PMA), in a temperature range encompassing the glass transition temperature, T_g. Activation energies for diffusion, E_D, were higher above Tg than below Tg for all four penetrants in PMA and in the structural isomer of PMA, poly(vinyl acetate) (PVA). For all penetrants studied, the Tg, the magnitude of the enthalpy of mixing (ΔH_m), as well as the E_D were all larger for PVA than for PMA. These differences were attributed to the stronger dipole-dipole interactions possible in PVA where the dipolar carbonyl group is separated from the chain backbone by an oxygen atom.

The carbonyl group in PMA is immediately adjacent and presumably sterically hindered by the chain backbone which suggests that PMA might be a stiffer molecule than PVA. Entropy considerations suggest that molecularly stiff polymers should be associated with small values of v Δα, ΔE_D, ΔE_D, ΔH_p, and (β), where v is the specific volume, Δα is the change in thermal expansivity about T_g, ΔH_p is the change in activation energy for diffusion about Tg, ΔE_D is the enthalpy of polymerization, and (β) is the logarithmic bulk relaxation rate constant of specific volume below T_g. These predictions appear to be satisfied for the systems of argon in PVC, PMA, PVA, and poly(ethyl methacrylate) (PEMA). The data suggest that PMA is a stiffer molecule than PVA. The weaker intermolecular forces of attraction and more hindered molecular rotations of PMA are consistent with a priori considerations of steric effects which have their origin in the fundamental structure of the PMA and PVA molecules.

The fraction of volume, φ, not occupied by polymer, estimated by several independent means for PMA at T_g, appears to be greater than that of PVA. Each of these two comparisons suggests that the molecular packing of PMA is more dense than the molecular packing of PVA.

The observed slow decrease in specific volume for PMA below Tg suggests that there could be regions throughout the polymer below Tg where the density is less than the equilibrium value. These predictions are consistent with the analyses of penetrant solubility below Tg which suggest that the molal volumes of the penetrants below Tg are larger than those above Tg. Also, analyses of the solubility data suggest that the enthalpies of mixing the noble gases in PMA tend to be exothermic below Tg. This suggests that below Tg, specific interactions occur between PMA and noble gas penetrants. The interactions are apparently manifested by decreases in free energy which are larger than expected for inert penetrants. The solubility and volumetric data appear to be consistent with the hypothesis that the polymer below Tg contains expanded, high-energy regions which preferentially absorb the diffusing penetrants.     

Selected States Magnetic Resonance Spectroscopy (SSMRS): Detection of Paramagnetic Element Dynamics

Abstract

Magnetic resonance (MR) response obtained in a strongly heterogeneous magnetic field with a linear gradient is analysed. It is shown that the employment of strong magnetic field gradients enables the MR spectroscopy to be accomplished in a system with selectively populated energy states (SSMRS). The method can be applied for measuring such physical quantities as the spin diffusion coefficient, D, spin-lattice, T_1m and spin-spin, T_2m, relaxation times and mobility, p_m, of paramagnetic elements in individual Zeeman energy states.

     

Effects of pressure and temperature on the solubility of monosodium L-glutamate monohydrate in water

Abstract

The solubility of monosodium L-glutamate monohydrate (MSG.H₂O) in water was measured at pressures in the range of 0.10-300MPa and 298.15K. The density of MSG solution at high concentrations and heat of solution at saturated concentration were also measured at atmospheric pressure. The solubility, m_s, increased with increasing pressure and the pressure coefficient, Θ_p, [?(? In m_s,? p)_T] at 0.10 MPa was (2.0 ± 0.1) × 10-¹⁰Pa-1. It agrees well with (2.1 ±0.2)× 10-¹⁰ Pa-¹ thermodynamically estimated using the partial molar volume, the activity coefficient of the solute in solution, and the molar volume of the crystal. The excellent agreement at 0.10MPa gives us confidence in the solubility data at higher pressures. The heat of solution data and other pertinent values were used to calculate the temperature coefficient of solubility, Θ_T [? (? In m_s/?(1/T))_p], by a thermodynamic equality. The resulting Θ_T compares well with the data directly measured by Ogawa.     

Cholesterol perturbs lipid bilayers nonuniversally

Cholesterol is well known to modulate the physical properties of biomembranes. Using modern x-ray scattering methods, we have studied the effects of cholesterol on the bending modulus K(C), the thickness D(HH), and the orientational order parameter S(xray) of lipid bilayers. We find that the effects are different for at least three classes of phospholipids characterized by different numbers of saturated hydrocarbon chains. Most strikingly, cholesterol strongly increases K(C) when both chains of the phospholipid are fully saturated but not at all when there are two monounsaturated chains.     

Exact diffusion coefficient of self-gravitating Brownian particles in two dimensions

We derive the exact expression of the diffusion coefficient of a self-gravitating Brownian gas in two dimensions. Our formula generalizes the usual Einstein relation for a free Brownian motion to the context of two-dimensional gravity. We show the existence of a critical temperature T_c at which the diffusion coefficient vanishes. For T < T_c, the diffusion coefficient is negative and the gas undergoes gravitational collapse. This leads to the formation of a Dirac peak concentrating the whole mass in a finite time. We also stress that the critical temperature T_c is different from the collapse temperature T_* at which the partition function diverges. These quantities differ by a factor 1-1/N where N is the number of particles in the system. We provide clear evidence of this difference by explicitly solving the case N = 2. We also mention the analogy with the chemotactic aggregation of bacteria in biology, the formation of “atoms” in a two-dimensional (2D) plasma and the formation of dipoles or “supervortices” in 2D point vortex dynamics.     

Effect of some statin group of drugs on the phase profile of liposomal membrane – a fluorescence anisotropy study

Using the fluorescent probe 1,6-diphenyl-1,3,5-hexatriene, we have investigated the effect of some statin group of drugs, widely used in hyperlipidemia, on the phase transition of model membranes such as dipalmitoyl phosphatidylcholine (DPPC) liposomes. The nature of the changes in the fluorescence anisotropy values suggested that the drugs simvastatin and mevastatin fluidized the membrane both before and after the phase transition temperature (T _m), whereas atorvastatin fluidized the membrane below T _m but rigidified the same above T _m, i.e., introduced an intermediate fluid condition within the lipid matrix. We have calculated the changes in van’t Hoff enthalpy values associated with the phase transitions due to chain melting in all the cases, and observed that the values of enthalpy decreased with increase in drug concentrations. In order to get a better insight, the fraction of motionally restricted lipid molecules was determined.     

代位合金中的空穴扩散和有序化

本文根据空穴扩散促使有序化的观点导出决定恒温有序化几率的一个公式。这个公式中包括扩散系数,柯诺库夫温度及其他实验都可以直接测定的数量。引用了现有的这些数量的实验数据,证明所提出的有序化几率公式和实验结果是符合的。     

An optimised molecular model for ammonia

Based on molecular dynamics (MD) computer simulations we investigate the dynamic behaviour of a model complex fluid suspension consisting of large (A) particles (the ‘solute’) immersed in a bath of smaller ‘solvent’ (B) particles. The goal is to identify the effect of systematic simplifications (coarse-graining) of the solvent on typical microscopic time correlation functions characterizing the single-particle and collective dynamics of the solute. As a reference system we employ a binary Lennard–Jones mixture of spherical particles with significant differences in particle sizes (σ_A>σ_B) and masses (m _A>m _B). We then replace the original B particles step by step by a reduced number of larger and heavier particles such that the mass and volume fraction of B particles is kept constant. At each step of coarse-graining, the intermolecular interactions between A particles are chosen such that the static A–A structure of the reference system is preserved. Our MD results indicate that coarse-graining has a profound influence on both the single-particle dynamics as reflected by the self-diffusion constant and the collective dynamics represented by the distinct part of the van Hove time correlation function. The latter holds only at intermediate packing fractions, whereas the collective dynamics turns out to be essentially insensitive to coarse-graining at high packing fractions.     

Spin-label HF-EPR of lipid ordering in cholesterol-containing membranes

Conventional oxazolidine spin-labelled lipids have the axial¹⁴N-hyperfine tensorz-axis directed along the long axis of the lipid chain. Investigation of lateral ordering of the lipids in membranes requires measurement of thex-y Zeeman anisotropy of the nonaxialg-tensor at high fields. Both the lateral and transverse ordering of the lipid chains in membranes of dimyristoyl phosphatidylcholine containing 40 mol% cholesterol in the liquid-ordered phase have been studied with 94 GHz electron paramagnetic resonance spectroscopy. This has been done by using probe amounts of phosphatidylcholine systematically spin-labelled at positionsn along the length of thesn- 2 chain [n-PCSL, 1-acyl-2-(n-(4,4-dimethyloxazolidine-N-oxyl) stearoyl)-sn-glycero-3-phosphocholine]. Nonaxial (g_xx?g_yy) anisotropy of the spin-labelled lipid chains is detected over a wide range of temperature throughout the liquid-ordered phase. The transverse profile of lateral ordering with position,n, of chain labelling follows the profile of the rigid steroid nucleus of cholesterol. It becomes progressively averaged towards the terminal methyl group of thesn- 2 chain, in the region of the flexible hydrocarbon chain of cholesterol. The nonaxial lipid ordering may be related to lipid domain formation in membranes containing cholesterol and saturated-chain lipids.     

TOF-SIMS analysis of adipose tissue from patients with chronic kidney disease

In this work, time-of-flight secondary ion mass spectrometry (TOF-SIMS) was used for detecting systematic variations in the spatial and compositional distributions of lipids in human tissue samples. Freeze-dried sections of subcutaneous adipose tissue from six chronic kidney disease (CKD) patients and six control subjects were analysed by TOF-SIMS using 25 keV Bi₃⁺ primary ions. Principal component analysis of signal intensities from different fatty acids, diacylglycerol and triacylglycerol ions showed evidence for systematic variations in the lipid distributions between different samples. The main observed difference in the spectra was a concerted variation in the signal intensities from the saturated lipids relative to the unsaturated lipids, while variations in the fatty acid chain lengths were considerably weaker. Furthermore, the three samples showing the lowest degree of saturation came from CKD patients, while three of the four samples with the highest degree of saturation were from control subjects, indicating that low saturation levels in the glycerol lipid distribution may be more frequent in patients with CKD. Systematic differences in the spatial distributions between saturated and unsaturated glycerol lipids were observed in several analysed areas.     

Magnetic Resonance Microscopy of Heterogeneity in Polymer Electrolyte Membranes

Magnetic resonance microscopy of Nafion 117 is used to measure the spatial variation of solvent dynamics in protonated (acid form) membranes immersed in solvent. Spatial resolution allows determination of membrane material property heterogeneity via T ₂ and diffusion variations to be easily studied in the presence of strong free solvent signal. Variation of T ₂ and diffusion as a function of solvent methanol–water mole fraction is measured. Spatially averaged T ₂ and diffusion data are in general agreement with previous bulk nuclear magnetic resonance studies; however, significant disparities from sample to sample at fixed solvent concentration are present in the spatially averaged data. The variation is determined to be due to changes in solvent mobility within the membrane over scales of the order of 10 mm, indicating macroscale heterogeneity of the solvent saturated membrane morphology. Authors' address: Sarah L. Codd, Department of Mechanical and Industrial Engineering, Montana State University, Bozeman, MT 59717-3800, USA     

In vivo lipid diffusion coefficient measurements in rat bone marrow

The diffusion coefficient of lipids, D_l, within bone marrow, fat deposits and metabolically active intracellular lipids in vivo will depend on several factors including the precise chemical composition of the lipid distribution (chain lengths, degree of unsaturation, etc.) as well as the temperature. As such, D_l may ultimately prove of value in assessing abnormal fatty acid distributions linked to diseases such as cystic fibrosis, diabetes and coronary heart disease. A sensitive temperature dependence of D_l may also prove of value for MR-guided thermal therapies for bone tumors or disease within other fatty tissues like the breast. Measuring diffusion coefficients of high molecular weight lipids in vivo is, however, technically difficult for a number of reasons. For instance, due to the much lower diffusion coefficients compared to water, much higher b factors than those used for central nervous system applications are needed. In addition, the pulse sequence design must incorporate, as much as possible, immunity to motion, susceptibility and chemical shift effects present whenever body imaging is performed. In this work, high b-factor line scan diffusion imaging sequences were designed, implemented and tested for D_l measurement using a 4.7-T horizontal bore animal scanner. The gradient set available allowed for b factors as high as 0.03 μs/nm² (30,000 s/mm²) at echo times as short as 42 ms. The methods were used to measure lipid diffusion coefficients within the marrow of rat paws in vivo, yielding lipid diffusion coefficients approximately two orders of magnitude smaller than typical tissue water diffusion coefficients. Phantom experiments that demonstrate the sensitivity of lipid diffusion coefficients to chain length and temperature were also performed.     

Short-time behavior of the kinetic spherical model with long-ranged interactions

The kinetic spherical model with long-ranged interactions and an arbitrary initial order m₀ quenched from a very high temperature to T is solved. In the short-time regime, the bulk order increases with a power law in both the critical and phase-ordering dynamics. To the latter dynamics, a power law for the relative order is found in the intermediate time-regime. The short-time scaling relations of small m₀ are generalized to an arbitrary m₀ and all the time larger than . The characteristic functions for the scaling of m₀ and for are obtained. The crossover between scaling regimes is discussed in detail. Received 17 September 1999     

Electrolyte interaction with DPPC vesicles: An ESR study

Summary The partition of the spin probe TEMPO between the fluid lipid phase of single-walled vesicles of dipalmitoylphosphatidylcholine and the aqueous bulk solution have been used to investigate the interaction of monovalent ions with polar head of neutral phospholipids. The study has been performed by electron spin resonance (ESR) spectroscopy in the temperature range of (20÷60)°C and in the presence of (0÷3) M 1∶1 electrolyte. In the absence of electrolyte the spin probe TEMPO reveals the characteristic order→disorder DPPC main phase transition atT _m≈37°C, while the pretransition occurs atT _p≈27.5°C. On increasing the ionic strength of the dispersion medium it results for the partition coefficient,P _C, that, at each temperature,P _C(3)>P _C(2)>P _C(1)>P _C(0). Correspondingly, the pretransition disappears and theT _m value downshifts from ≈37°C with 0 M electrolyte to ≈34°C with 3M salt in the order:T _m(3)>T _m(2)>T _m(1)>T _m(0). The results suggest an increase in the net surface charge density of vesicles due to high ionic-strength values. The alteration of the electric interactions occurring into the polar zone of DPPC bilayer reduces the hindrances which, in turn, favour the enhancement of TEMPO partitioning in the hydrophobic core of phospholipid bilayers. The authors of this paper have agreed to not receive the proofs for correction.