组分混合磷脂球胶束化动力学

两亲性磷脂分子能够形成各种不同形态的胶束,其结构形成不仅依赖于磷脂分子结构和组成,还依赖于两亲性分子的自组装路径. 本工作采用粗粒化分子动力学方法模拟研究了二棕榈酰磷脂酰胆碱(DPPC)与十六烷基磷酸胆碱(HPC)混合磷脂球胶束化行为. 通过调节DPPC/HPC的组分比例和磷脂球尺寸,观察到多种不同胶束结构形成,例如：球形和非球形(扁平或长椭球)囊泡、盘形胶束、单环或双环胶束和蠕虫状胶束. 研究发现,由于原位胶束化作用,采用磷脂球作为初始态有利于形成囊泡和环形拓扑结构胶束. 模拟结果表明,结合初始态结构设定同时调节磷脂分子组成是一种有效调控磷脂胶束结构的方法.     

蜂毒肽浓度和磷脂组分对巨囊泡泄露的影响

蜂毒肽作为一种广谱抗菌肽已经得到广泛认知,用蜂毒肽构建载药体系攻击癌细胞研究正在兴起.基于仿生物膜模型探索其破坏机理,可以避免潜在活性细胞过程的影响.在此,我们选用细胞尺寸的单层巨囊泡膜模型,可在光学显微镜下直接观察和操作,获得仿正常细胞膜和仿癌细胞膜在不同蜂毒肽浓度刺激下的响应.研究得出,低浓度蜂毒肽诱导囊泡泄露实验表明中性磷脂囊泡以孔模式为主泄露,负电性磷脂囊泡以爆裂模式为主泄露;高浓度蜂毒肽诱导囊泡泄露实验表明负电性磷脂相较于中性磷脂可延迟蜂毒肽作用效果;蜂毒肽色氨酸残基荧光光谱表明囊泡膜表面蜂毒肽吸附量以及泄露模式依赖于磷脂组分.此外,推断了蜂毒肽对不同组分磷脂膜的破坏作用模型.研究为蜂毒肽在肿瘤细胞的作用机制及其衍生物的优化设计提供参考.     

蜂毒肽浓度和磷脂组分对巨囊泡泄露的影响

蜂毒肽作为一种广谱抗菌肽已经得到广泛认知,用蜂毒肽构建载药体系攻击癌细胞研究正在兴起.基于仿生物膜模型探索其破坏机理,可以避免潜在活性细胞过程的影响.在此,我们选用细胞尺寸的单层巨囊泡膜模型,可在光学显微镜下直接观察和操作,获得仿正常细胞膜和仿癌细胞膜在不同蜂毒肽浓度刺激下的响应.研究得出,低浓度蜂毒肽诱导囊泡泄露实验表明中性磷脂囊泡以孔模式为主泄露,负电性磷脂囊泡以爆裂模式为主泄露;高浓度蜂毒肽诱导囊泡泄露实验表明负电性磷脂相较于中性磷脂可延迟蜂毒肽作用效果;蜂毒肽色氨酸残基荧光光谱表明囊泡膜表面蜂毒肽吸附量以及泄露模式依赖于磷脂组分.此外,推断了蜂毒肽对不同组分磷脂膜的破坏作用模型.研究为蜂毒肽在肿瘤细胞的作用机制及其衍生物的优化设计提供参考.     

荧光猝灭法对超支化聚合物囊泡温敏性翻转的研究

本文利用稳态瞬态荧光光谱法对硝酸铊猝灭芘标记超支化聚合物囊泡的机理进行了探讨,并将猝灭实验应用于超支化聚合物囊泡温敏性翻转的研究。结果发现,硝酸铊对芘标记超支化聚合物囊泡的猝灭属于动态过程,并且有选择性地猝灭囊泡双分子层的外层;聚合物链段温敏性的转变,引起该链段在囊泡双分子层间的再分布,从而导致超支化聚合物囊泡翻转。     

磷脂囊泡在胺端基和羧端基修饰金表面的沉积

磷脂囊泡与阴, 阳离子性表面作用的深入理解对磷脂的生物纳米科技应用具有重要意义. 通过石英电子微天平及耗散系数测量仪, 研究了不同离子性磷脂囊泡在胺端基和羧端基修饰Au衬底的沉积行为. 实验观察到四条囊泡沉积路径: (ⅰ)吸附至临界值后破裂成膜; (ⅱ)吸附即破裂成膜; (ⅲ)吸附不破裂; (ⅳ)不吸附. 沉积路径由囊泡与衬底的双电层相互作用决定, 离子可发挥调节作用.     

磷脂囊泡在胺端基和羧端基修饰金表面的沉积

磷脂囊泡与阴,阳离子性表面作用的深入理解对磷脂的生物纳米科技应用具有重要意义.通过石英电子微天平及耗散系数测量仪,研究了不同离子性磷脂囊泡在胺端基和羧端基修饰Au衬底的沉积行为.实验观察到四条囊泡沉积路径:(ⅰ)吸附至临界值后破裂成膜;(ⅱ)吸附即破裂成膜;(ⅲ)吸附不破裂;(ⅳ)不吸附.沉积路径由囊泡与衬底的双电层相互作用决定,离子可发挥调节作用.     

蜂毒肽与多组分生物膜作用：电性与相态的影响

蜂毒肽非特异性地靶向杀伤细菌具有重要的生物医学应用前景. 利用荧光光谱与荧光显微考察了蜂毒肽与单组分、多组分磷脂膜的作用机制. 发现对于不同电性与相态的磷脂膜, 肽-膜作用呈现为稳定桶板型孔、非稳U型孔及变薄裂解等多种机制, 具有显著不同的内含物泄露效率. 多组分磷脂囊泡的泄露实验表明, 泄露由肽亲和性较强的磷脂组分决定. 相较于凝胶相磷脂, 蜂毒肽与液相磷脂的亲和性强, 凝胶-液相混合囊泡与纯液相磷脂囊泡的泄露性质相近; 相较于双电性磷脂, 蜂毒肽与负电性磷脂的亲和性强, 双电-负电混合囊泡与纯负电磷脂囊泡的泄露性质相近. 研究深化了多肽与多组分生物膜作用机制的理解.     

磷脂在膜结构间的交换:温度和离子强度的影响

磷脂跨膜交换对生物膜功能与药学研究有重要意义.石英电子微天平及耗散系数测量仪被用于研究囊泡与支撑膜间磷脂的交换行为.研究表明:首先,在磷脂跨膜输运过程中,热力学环境和离子强度对支撑膜表面吸附囊泡的形变程度影响较小,囊泡与支撑膜的总接触面积直接取决于囊泡的吸附数量;其次,交换过程中膜结构间最大总接触面积随着温度的升高和离子强度的降低而增大,温度和离子引起的囊泡吸附速率和跨膜交换速率的变化在其中发挥着关键调节作用.本研究有助于加深对磷脂在生理条件下跨膜输运过程的理解,并为基于脂质体的药物载运体系研究提供参考.     

X射线小角散射研究温度对DNA/磷脂复合物结构的影响

报道由短链DNA和磷脂分子在水溶液中形成的复合物的小角散射研究结果. 水溶液中, DNA分子和阳性磷脂分子自发组装成有序的复合多层膜结构: 脂双层相互平行, DNA夹在脂双层之间, 在垂直于DNA方向呈现一维有序结构. 逐渐升高体系的温度, 磷脂双分子膜柔软增加, DNA向双分子层内塌陷, 使多层膜层间距逐渐减小. 而由于DNA分子是一种刚性分子, DNA之间的距离在所测温度 范围内没有变化.     

粗粒化模型中的Gay-Berne相互作用势

合理描述非球形粗粒化粒子间的相互作用是提高粗粒化分子动力学模拟速度的关键.为此本文介绍了Gay-Berne势.将之应用于两种有机小分子体系,在合理选择构象集后,由遗传算法得到了粗粒化粒子的GB参数,并通过对粗粒化模型和全原子模型得到的范德瓦耳斯相互作用的对比检验了GB力场参数.最后,指出如何处理作用位点是粗粒化模型发展的一个关键问题.     

在相反电荷表面活性剂存在下阳离子瓜尔胶水溶液流变行为

合成了阳离子瓜尔胶(CG),研究了其水溶液在十二烷基硫酸钠(SDS)存在下的流变行为．测定结果表明,随SDS浓度的增加,溶液零切黏度增加了3个数量级以上．小幅振荡剪切实验结果表明模量几乎和SDS浓度无关,但是驰豫时间则随着SDS浓度增加而迅速增加．因此,SDS的加入将会使交联点的强度增加,但是不会改变交联点密度．SDS对CG流变行为的影响可以用两阶段模型加以描述．在SDS存在下CG水溶液流变行为主要受到由SDS胶束形成的交联点的控制．根据Arrhenius公式得到的瓜儿胶水溶液的流动活化能在将SDS分子疏水尾端从胶束移到水相之中所需能量是一致的.     

Structure of symmetric and asymmetric "ripple" phases in lipid bilayers

We reproduce the symmetric and asymmetric "rippled" P(beta') states of lipid membranes by Monte Carlo simulations of a coarse-grained molecular model for lipid-solvent mixtures. The structure and properties compare favorably with experiments. The asymmetric ripple state is characterized by a periodic array of fully interdigitated "defect" lines. The symmetric ripple state maintains a bilayer structure, but is otherwise structurally similar. The main force driving the formation of both ripple states is the propensity of lipid molecules with large head groups to exhibit splay.     

The role of hydrophobic interaction in phase transition and structure formation of lipid membranes and proteins

The hydrophobic interaction arises from the ordered structure of water around nonpolar groups of molecules in an aqueous solvent. Because biological systems are made of various macromolecules and amphiphiles which are suspended in aqueous solution, the hydrophobic interaction plays a very important role in the formation of higher-order structure and phase transitions in biological systems. Considering the hydrophobic interaction, the van der Waals interaction and the entropic effect, an equation of state of a lipid membrane was obtained which was analogous to the van der Waals equation. The characteristics of the lipid bilayer phase transition as well as the phase behaviors of a lipid monolayer were explained by this equation of state. Experimental evidence was obtained from ultrasonic measurements which indicated that its phase transition accompanys significant critical phenomena. Analysis of the hydrophobicity of amino acid sequences revealed that the morphology of the proteins was determined by the hydrophobicity alone. The essential role of the hydrophobic interaction in the morphogenesis of proteins could be confirmed by a denaturation experiment on a soluble protein, carbonic anhydrase B. Fluorescence measurements showed that an intermediate state, the so-called molten globule state, had a quite hydrophobic core, indicating that the globule shape of this protein is stabilized by the hydrophobic interaction.     

Debye-Hückel theory for slab geometries

The electrostatic interaction of charged particles through or at a low-dielectric slab, such as a lipid bilayer immersed in water or a self-assembled monolayer (SAM) on a metal substrate, is considered theoretically in the presence of salt within the Gaussian approximation using a generalized Green's formalism. A number of separate situations are discussed: i) The presence of a low-dielectric slab leads to pronounced interactions of a single charge with the slab via the formation of polarization surface charges. For SAMs on metal substrates, there is an intricate crossover from image-charge attraction to the metal substrate (for large distances) to image-charge repulsion from the SAM (for small distances) with a stable minimum at a distance of roughly 20 times the thickness of the hydrophobic film. For bilayers in water, the interaction of a single charge is always repulsive. ii) The surface potential of a SAM is calculated for the case when the hydrophobic layer contains dipole moments, which might explain the recently observed long-ranged repulsion of hydrophobic scanning tips from PEG-terminated SAMs on gold. iii) The interaction between charged particles through the bilayer is weakened. Oppositely charged particles still attract each other through the membrane. The free-energy minimum occurs as a result of the competition between self-repulsion from the slab and interparticle attraction and is located at a separation from the membrane surface which equals 15 times the membrane thickness. iv) Surface charges on the two surfaces of a bilayer attract each other through the bilayer unless the surface charge densities are the same, even if the signs are the same. v) All these effects are strongly influenced by the presence of salt. Received 25 January 2000     

磷酸钾缓冲溶液与模型细胞膜相互作用的和频光谱

利用和频光谱技术详细研究了磷酸钾缓冲溶液与带负电荷的生物仿生膜(d₅₄-DMPG磷脂双层膜)相互作用的实时过程．通过监控CD₂、CD₃、磷脂分子头部的磷酸根以及羰基官能团的光谱信号随加入磷酸钾缓冲溶液的实时变化,获得了磷脂双层膜分子结构的动力学变化．结果表明K⁺能够结合到细胞膜上,并且很快地引起了CD₂、CD₃、磷脂头部磷酸根以及羰基官能团信号的变化．根据各官能团的和频信号响应,磷酸钾缓冲溶液很可能是通过在双层膜中形成环形气孔来与磷脂双层膜发生作用．该结果可以很好地解释磷酸钾缓冲溶液环境下的离子协助蛋白质的跨膜过程．     

Fluorescence Study of Lipid Bilayer Interactions of Eu(III) Coordination Complexes

The interaction between Eu(III) tris-β-diketonato coordination complexes (EC), displaying antitumor activity, and lipid vesicles composed of zwitterionic lipid phosphatidylcholine has been studied using fluorescence spectroscopy techniques. To characterize EC-membrane binding, several fluorescent probes, including pyrene, Prodan and 1,6-diphenyl-1,3,5-hexatriene, have been employed. It has been found that EC display effective partitioning into lipid phase, giving rise to structural modifications of both polar and nonpolar lipid bilayer regions, viz. enhancement of membrane hydration and increase in tightness of lipid chain packing. The fact that EC accumulating in lipid bilayer are incapable of inducing significant disruption of membrane structural integrity creates strong prerequisites for development of liposomal nanocarriers of these potential antitumor drugs. Such a possibility is also corroborated by the observation that EC membrane incorporation does not prevent lipid bilayer partitioning of long-wavelength squaraine dyes which represent promising candidates for visualization of liposome biodistribution.     

Representing environment-induced helix-coil transitions in a coarse grained peptide model

Coarse grained (CG) models are widely used in studying peptide self-assembly and nanostructure formation. One of the recurrent challenges in CG modeling is the problem of limited transferability, for example to different thermodynamic state points and system compositions. Understanding transferability is generally a prerequisite to knowing for which problems a model can be reliably used and predictive. For peptides, one crucial transferability question is whether a model reproduces the molecule's conformational response to a change in its molecular environment. This is of particular importance since CG peptide models often have to resort to auxiliary interactions that aid secondary structure formation. Such interactions take care of properties of the real system that are per se lost in the coarse graining process such as dihedral-angle correlations along the backbone or backbone hydrogen bonding. These auxiliary interactions may then easily overstabilize certain conformational propensities and therefore destroy the ability of the model to respond to stimuli and environment changes, i.e. they impede transferability. In the present paper we have investigated a short peptide with amphiphilic EALA repeats which undergoes conformational transitions between a disordered and a helical state upon a change in pH value or due to the presence of a soft apolar/polar interface. We designed a base CG peptide model that does not carry a specific (backbone) bias towards a secondary structure. This base model was combined with two typical approaches of ensuring secondary structure formation, namely a C_α-C_α-C_α-C_α pseudodihedral angle potential or a virtual site interaction that mimics hydrogen bonding. We have investigated the ability of the two resulting CG models to represent the environment-induced conformational changes in the helix-coil equilibrium of EALA. We show that with both approaches a CG peptide model can be obtained that is environment-transferable and that correctly represents the peptide's conformational response to different stimuli compared to atomistic reference simulations. The two types of auxiliary interactions lead to different kinetic behavior as well as to different structural properties for fully formed helices and folding intermediates, and we discuss the advantages and disadvantages of these approaches.     

A molecular model for the line tension of lipid membranes

The line tension of a symmetric, lipid bilayer in its liquid-crystalline state is calculated on the basis of a molecular lipid model. The lipid model extends the opposing forces model by an expression for the conformational free energy of the hydrocarbon chains. We consider a membrane edge that consists of a perturbed bilayer covered by a section of a cylinder-like micelle. The structural rearrangement of the lipids implies an excess free energy which we minimize with respect to the cross-sectional shape of the membrane edge, including both the micellar and the bilayer region. The line tension is derived as a function of molecular lipid properties, like the lipid chain length or the head group interaction strength. We also relate it to the spontaneous curvature of the lipid layer. We find the line tension to become smaller for lipid layers that tend to curve more towards the hydrophobic core. Our predictions for the line tension and their relation to experimentally derived values are discussed. Received 2 January 2000     

Examining Protein-Lipid Interactions in Model Systems with a New Squarylium Fluorescent Dye

The applicability of newly synthesized squarylium dye Sq to probing the changes in physical characteristics of lipid bilayer on the formation of protein-lipid complexes has been evaluated. Lipid vesicles composed of zwitterionic phospholipid phosphatidylcholine (PC) and its mixtures with positively charged detergent cetyltrimethylammonium bromide (CTAB), anionic phospholipid cardiolipin (CL), and cholesterol (Chol) were employed as lipid component of model membrane systems while protein constituent was represented by lysozyme (Lz). Fluorescence intensity of Sq was found to decrease on Lz association with lipid bilayer. This effect was observed in all kinds of model systems suggesting that Sq is sensitive to modification of lipid bilayer physical properties on hydrophobic protein-lipid interactions. It was found that Sq spectral response to variations in Chol content depends on relative contributions of electrostatic and hydrophobic components of Lz-membrane binding.     

A molecular-dynamics study of oscillations of unclosed crystal nanostructures based on bilayer metal films

Behavior of unclosed nanostructures is investigated in the course of their formation from bilayer films of a Ni–Cu system with crystal structure. The investigation is performed on the basis of the molecular dynamics method using a many-body potential of interatomic interaction. It is shown that the edges of an unclosed nanostructure produced from a bilayer metal film can perform free harmonic oscillations. The dependence of the oscillation amplitude of the nanostructure on the size of the initial film is investigated. Optimum geometrical parameters of the initial film are determined in order to form unclosed nanostructures oscillating with maximum amplitude. The results obtained are promising for the development of components for nanodevices of different types and applications.