包膜颗粒的表面磷脂重排对细胞内吞的影响

在纳米颗粒表面包裹生物膜可以增强体系的生物相容性、靶向性、内含物释放的可控性,但包膜颗粒与细胞膜作用的机制仍不清楚.在本研究中,我们考察了不同侧向流动性的负电性磷脂膜包裹的多孔硅纳米颗粒的体外细胞内吞行为.发现,高流动的液态磷脂包被产生了较高的内吞效率,并且它的内吞方式也与低流动的凝胶态磷脂包被情况存在差异.Derjaguin-Landau-Verway-Overbeek理论分析表明,前者的磷脂空间重排能够促进生物膜与细胞膜的融合与粒子内吞,而后者在膜融合过程中存在高能量势垒,因此只能以胞饮的方式被动地进入细胞.我们的研究深化了包膜粒子内吞过程的认识,为后续设计复杂的纳米载药体提供了新的思路和参考.     

包膜颗粒的表面磷脂重排对细胞内吞的影响

在纳米颗粒表面包裹生物膜可以增强体系的生物相容性、靶向性、内含物释放的可控性,但包膜颗粒与细胞膜作用的机制仍不清楚.在本研究中,我们考察了不同侧向流动性的负电性磷脂膜包裹的多孔硅纳米颗粒的体外细胞内吞行为.发现,高流动的液态磷脂包被产生了较高的内吞效率,并且它的内吞方式也与低流动的凝胶态磷脂包被情况存在差异.Derjaguin-Landau-Verway-Overbeek理论分析表明,前者的磷脂空间重排能够促进生物膜与细胞膜的融合与粒子内吞,而后者在膜融合过程中存在高能量势垒,因此只能以胞饮的方式被动地进入细胞.我们的研究深化了包膜粒子内吞过程的认识,为后续设计复杂的纳米载药体提供了新的思路和参考.     

重力对金纳米颗粒在生物膜表面吸附影响的荧光研究

纳米颗粒在生物膜表面的吸附行为是纳米生物技术领域的重要问题. 采用正、倒置实验, 通过荧光显微镜定量研究了重力对金纳米颗粒在支撑磷脂膜表面吸附的影响. 研究发现, 颗粒尺寸决定其在顶或底层支撑膜表面吸附的差异性. 吸附量的差异与颗粒的沉淀速率和扩散速率之比的对数呈线性关系. 粒径小于14 nm时, 不考虑重力在吸附时的影响; 粒径大于176 nm时, 重力在吸附中占主导地位. 为药物载体研究和理解颗粒－生物膜相互作用提供参考.     

自组装银膜增强8-羟基喹啉铝(Alq_3)光致发光的实验和理论研究

实验和理论研究了不同自组装密度的银纳米颗粒膜对8-羟基喹啉铝(Alq_3)光致发光的影响,结果表明:Alq_3光致发光的表观增强和发射增强因子与银纳米颗粒膜密度呈正相关关系,最大值约为3.2和13;理论计算表明银纳米颗粒膜对Alq_3光致发光的量子效率和发射的最大增强因子约为1.4和15,对比实验和理论结果,金属纳米颗粒膜的近场场强增强是导致Alq3光致发光发射强度增强的主要因素,且Alq_3光致发光效率与Alq_3相对银纳米颗粒的分布和"热点"区域面积覆盖率有关。     

重力对金纳米颗粒在生物膜表面吸附影响的荧光研究

纳米颗粒在生物膜表面的吸附行为是纳米生物技术领域的重要问题.采用正、倒置实验,通过荧光显微镜定量研究了重力对金纳米颗粒在支撑磷脂膜表面吸附的影响.研究发现,颗粒尺寸决定其在顶或底层支撑膜表面吸附的差异性.吸附量的差异与颗粒的沉淀速率和扩散速率之比的对数呈线性关系.粒径小于14 nm时,不考虑重力在吸附时的影响;粒径大于176 nm时,重力在吸附中占主导地位.为药物载体研究和理解颗粒-生物膜相互作用提供参考.     

十八胺LB膜吸附组装金纳米颗粒研究

制备了十八胺单层、多层LB膜及粒径为几个纳米的金纳米粒子。pH值小于10.3时十八胺带正电荷,将其置于金纳米溶胶(pH值10.3)中,带负电荷的金纳米粒子与带正电荷的十八胺之间通过静电作用,金纳米颗粒被成功地吸附组装到十八胺LB膜中,形成纳米薄膜。紫外-可见光谱、红外光谱及扫描电镜显示:金纳米颗粒通过这种方法能够很好的组装在十八胺LB膜上,且其组装层整齐有序,同时也受十八胺LB膜层数及组装时间的影响。     

磷脂跨膜交换机制的研究

膜间磷脂交换是一项重要的生理活动, 其对药物运输及膜功能研究有重要意义. 本文用石英晶体微天平及耗散系数测试仪研究囊泡与囊泡、囊泡与支撑膜间磷脂交换行为, 荧光光谱仪用来测量膜表面电性与膜组分对磷脂交换的影响. 实验结果表明: 磷脂跨膜交换速率与交换时间成反比, 膜表面异电性磷脂的增加会加速膜内相互作用和磷脂跨膜交换速率, 以及改变膜表面组分会对囊泡与支撑膜间的磷脂交换产生影响. 本文研究有助于加深理解磷脂跨膜交换机制, 并对药学研究提供参考.     

磷脂跨膜交换机制的研究

膜间磷脂交换是一项重要的生理活动,其对药物运输及膜功能研究有重要意义.本文用石英晶体微天平及耗散系数测试仪研究囊泡与囊泡、囊泡与支撑膜间磷脂交换行为,荧光光谱仪用来测量膜表面电性与膜组分对磷脂交换的影响.实验结果表明:磷脂跨膜交换速率与交换时间成反比,膜表面异电性磷脂的增加会加速膜内相互作用和磷脂跨膜交换速率,以及改变膜表面组分会对囊泡与支撑膜间的磷脂交换产生影响.本文研究有助于加深理解磷脂跨膜交换机制,并对药学研究提供参考.     

蛋白质对纳米铕岛膜表面荧光的增强作用

将经硫辛酸修饰的铕纳米颗粒和蛋白质固定在石英玻璃表面或胶原蛋白隔离的石英玻璃表面,研究蛋白质对纳米铕岛膜荧光的增强作用.研究结果发现,在275nm激发波长下,铕纳米岛膜的荧光光谱与铕纳米颗粒溶液的荧光性质相似,且微量蛋白质的加入可以使铕纳米岛膜的荧光强度增强,但被石英玻璃片吸附后,铕纳米岛膜以及铕-蛋白质体系的荧光发射峰的位置由378.8nm红移至420nm,且胶原蛋白隔离铕纳米岛膜和滴加微量BSA蛋白质的荧光光谱相似,但荧光强度没有发生明显变化.     

多纳米粒子穿越磷脂膜

本文采用耗散粒子动力学模拟方法研究了多纳米粒子与溶液中的磷脂膜相互作用. 模拟中选择纳米颗粒的形状分别为球状和柱状,并且在动力学过程中给它们设置了不同的初始速度. 根据纳米粒子穿膜在动力学过程中体现出不同的特性,分别定义了几种粒子穿越磷脂的模式,并且基于粒子之间的相互作用强度和粒子初始速度,描绘了穿膜模式的详细相图. 本文还进一步研究了体系能量、迴旋半径等参数在不同穿越模式中的动力学过程. 研究结果有助于人们理解纳米颗粒穿膜在生命活动过程中的作用.     

Collective motion of polar active particles on a sphere

Collective motion of active particles with polar alignment is investigated on a sphere. We discussed the factors that affect particle swarm motion and define an order parameter that can show the degree of particle swarm motion. In the model, we added a polar alignment strength, along with Gaussian curvature, affecting particles swarm motion. We find that when the force exceeds a certain limit, the order parameter will decrease with the increase of the force. Combined with our definition of order parameter and observation of the model, the reason is that particles begin to move side by side under the influence of polar forces. In addition, the effects of velocity, rotational diffusion coefficient, and packing fraction on particle swarm motion are discussed. It is found that the rotational diffusion coefficient and the packing fraction have a great influence on the clustering motion of particles, while the velocity has little influence on the clustering motion of particles.     

Comprehensive studies on the interactions between chitosan nanoparticles and some live cells

As more and more oral formulations of nanoparticles are used in clinical contexts, a comprehensive study on the mechanisms of interaction between polymer nanoparticles and live cells seems merited. Such a study was conducted and the results were compared to the polymer itself in order to demonstrate different kinds of effects that are brought into the cell by polymer and its nanoparticles, especially the effects on the biomembrane. Several techniques, including surface plasmon resonance (SPR), Fourier transformed infrared spectroscopy (FTIR), Raman spectroscopy, fluorescence polarization spectroscopy (FP), flow cytometry (FCM) with quantitative analysis, and confocal images with antibody staining were employed toward this end. The cytotoxicity in vitro was also evaluated. Chitosan (CS), a polycationic polymer, was used to prepare the nanoparticles. We demonstrate that chitosan nanoparticles (CS-NP) induce strong alterations in the distribution of membrane proteins, fluidity of membrane lipids, and general membrane structure. Furthermore, the uptake of CS-NP into Caco-2 cells was found to have a similar mechanism to that of CS molecules, but the differences in degree were noted. These results indicate that positive charge and nanoscale size were the factors that most significantly affected the interactions between the nanoparticles of polycationic polymers and live cells. However, no difference in cytotoxicity toward the Caco-2 cells was found between CS and CS-NP. This supports the idea that CS-NP is an effective and safe carrier for oral drug delivery.     

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.     

Molecular dynamics study of the infiltration of lipid-wrapping C60 and polyhydroxylated single-walled nanotubes into lipid bilayers

Because of the many potential medical applications of nanoparticles, considerable research has been conducted on the interactions between nanoparticles and biomembranes. We employed coarsegrained molecular dynamics simulations to study the infiltration of lipid-wrapping C₆₀ and polyhydroxylated single-walled nanotubes. Diffusion coefficients and scaling factors are adopted to quantify the diffusivity of the biomembranes, and the rupture tension is used to measure the lateral strength of the lipid bilayer. According to our simulations, all wrapped nanoparticles, except those wrapped by dipalmitoyl-glycero-phosphoglycerol, can be inserted into the bilayers. Our simulations also reveal that the bilayers remain in free diffusion after the nanoparticle insertions while their diffusion coefficient can be altered significantly. The polyhydroxylated single-walled nanotubes lead to significant changes to the lateral strength of biomembranes and this effect depends on the quantity of the inserted nanoparticles. The simulations demonstrate the feasibility of using these methods to deliver nanoparticles while some suggestions are given for choosing the appropriate lipids for wrapping. The results also suggest that the functionalized nanoparticles could be applied in strengthening or weakening the lateral strength of biomembranes for specific purposes.     

Biophysical changes induced by cholesterol on phosphatidylcholine artificial biomembranes containing alamethicin oligomers

Cholesterol is an important constituent of eukaryotic cell membranes, whose interaction with phospholipids leads to a broad range of biological roles, such as: maintenance of proper fluidity, formation of raft domains, reduction of passive permeability of various chemical species through the bilayer (e.g., glucose, glycerol, K⁺, Na⁺ and Cl⁻ ions), and increased mechanical strength of the membrane. In this work we studied an interesting paradigm, as to whether cholesterol-containing phosphatidylcholine biomembranes influence the kinetics and transport features of alamethicin oligomers embedded into it. We demonstrate that moderate relative amounts of cholesterol increase the electrical conductance of various sub-conductance states of the alamethicin oligomer, caused probably by a non-monotonic change in the lumped dipole moment of the biomembrane. Our data suggest that biomembrane stiffness caused by cholesterol, visibly modifies the association-dissociation rates of alamethicin oligomerization in the biomembrane. Moreover, increasing concentrations of cholesterol seem to lead to more stable intermediate alamethicin oligomers. We show that in the presence of cholesterol, as the diameter of the alamethicin oligomer increases, so does the time of another monomer to get picked up. These results brings into focus the interesting issue of how oligomerization of proteins affects their interaction affinities for membrane-based lipids.     

Controlled flame synthesis of αFe<Subscript>2</Subscript>O<Subscript>3</Subscript> and Fe<Subscript>3</Subscript>O<Subscript>4</Subscript> nanoparticles: effect of flame configuration,flame temperature,and additive loading

Superparamagnetic iron oxide nanoparticles are used in diverse applications, including optical magnetic recording, catalysts, gas sensors, targeted drug delivery, magnetic resonance imaging, and hyperthermic malignant cell therapy. Combustion synthesis of nanoparticles has significant advantages, including improved nanoparticle property control and commercial production rate capability with minimal post-processing. In the current study, superparamagnetic iron oxide nanoparticles were produced by flame synthesis using a coflow flame. The effect of flame configuration (diffusion and inverse diffusion), flame temperature, and additive loading on the final iron oxide nanoparticle morphology, elemental composition, and particle size were analyzed by transmission electron microscopy (TEM), high-resolution TEM (HR-TEM), energy dispersive spectroscopy (EDS), and Raman spectroscopy. The synthesized nanoparticles were primarily composed of two well known forms of iron oxide, namely hematite αFe₂O₃ and magnetite Fe₃O₄. We found that the synthesized nanoparticles were smaller (6–12 nm) for an inverse diffusion flame as compared to a diffusion flame configuration (50–60 nm) when CH₄, O₂, Ar, and N₂ gas flow rates were kept constant. In order to investigate the effect of flame temperature, CH₄, O₂, Ar gas flow rates were kept constant, and N₂ gas was added as a coolant to the system. TEM analysis of iron oxide nanoparticles synthesized using an inverse diffusion flame configuration with N₂ cooling demonstrated that particles no larger than 50–60 nm in diameter can be grown, indicating that nanoparticles did not coalesce in the cooler flame. Raman spectroscopy showed that these nanoparticles were primarily magnetite, as opposed to the primarily hematite nanoparticles produced in the hot flame configuration. In order to understand the effect of additive loading on iron oxide nanoparticle morphology, an Ar stream carrying titanium-tetra-isopropoxide (TTIP) was flowed through the outer annulus along with the CH₄ in the inverse diffusion flame configuration. When particles were synthesized in the presence of the TTIP additive, larger monodispersed individual particles (50–90 nm) were synthesized as observed by TEM. In this article, we show that iron oxide nanoparticles of varied morphology, composition, and size can be synthesized and controlled by varying flame configuration, flame temperature, and additive loading.     

Limited slowdown of endocrine-disruptor diffusion in confined fluid lipid membranes

Self-diffusion rates of lipids and trapped bisphenol A (BPA) are determined in various sizes of confined but fluid membranes by high-field-gradient NMR at 600 MHz. Micelles and vesicles of 3- to 400-nm diameters are used as model membranes to get an insight into the molecular diffusion in such soft environments. The slowdown of BPA and lipid motions is leveled off in 100- and 400-nm vesicles, although the hydrodynamic continuum model gives the aggregate motion slowed inversely to the aggregate size. Instead, the limited motion is related to the intra-membrane fluidity.     

Nanoparticle Polydispersity Can Strongly Affect In Vitro Dose

When nanomaterials meet the biological world, the cellular interaction of nanoparticles is routinely assessed in in vitro systems. Establishing dose–response relationships requires that the dose of nanoparticles delivered to the cell is accurate and precise. Nanoparticles as such or coated with high molecular‐weight compounds are rarely uniform and the influence of heterogeneity, including polydispersity both in size and mass density, on the delivered dose is never studied before. Furthermore, a probabilistic term describing particle adherence to cells is introduced and the importance is discussed. By tracing the movement of discrete particles via modeling, it is found that the influence of heterogeneity cannot be neglected when the average particle size promotes settling over diffusion. However, the influence of polydispersity on the delivered cellular dose is less critical for particulate systems whose mean size promotes diffusion. The influence of a non‐instantaneous particle association to the cell is negligible for particles whose motion is dominated by settling, but it is relevant for small particles whose motion is governed by diffusion.     

Lateral diffusion in equimolar mixtures of natural sphingomyelins with dioleoylphosphatidylcholine

Cellular membranes of mammals are composed of a complex assembly of diverse phospholipids. Sphingomyelin (SM) and phosphatidylcholine (PC) are important lipids of eukaryotic cellular membranes and neuronal tissues, and presumably participate in the formation of membrane domains, known as "rafts," through intermolecular interaction and lateral microphase decomposition. In these two-dimensional membrane systems, lateral diffusion of lipids is an essential dynamic factor, which might even be indicative of lipid phase separation process. Here, we used pulsed field gradient nuclear magnetic resonance to study lateral diffusion of lipid components in macroscopically oriented bilayers composed of equimolar mixtures of natural SMs of egg yolk, bovine brain, bovine milk and dipalmitoylphosphatidylcholine (DPPC) with dioleoylphosphatidylcholine (DOPC). In addition, differential scanning calorimetry was used as a complementary technique to characterize the phase state of the lipid bilayers. In fully liquid bilayers, the lateral diffusion coefficients in both DOPC/DPPC and DOPC/SM systems exhibit mean values of the pure bilayers. For DOPC/SM bilayer system, this behavior can be explained by a model where most SM molecules form short-lived lateral domains with preferential SM-SM interactions occurring within them. However, for bilayers in the presence of their low-temperature gel phase, lateral diffusion becomes complicated and cannot simply be understood solely by a simple change in the liquid phase decomposition.