Coarse-grained molecular dynamics simulation of interactions between cyclic lipopeptide Bacillomycin D and cell membranes

According to experimental studies, Bacillomycin D has strong antimicrobial activities, but the antimicrobial mechanism is still unknown. In this paper, the interaction mechanisms between this cyclic lipopeptide and three different charged cell membranes are studied via Coarse-Grained Molecular Dynamics (CG MD) simulations. A specific CG model for the cyclic lipopeptide Bacillomycin D was developed. The insertion of cyclic lipopeptide Bacillomycin D into DOPC, DOPC/DPPA and DOPC/DOTAP cell membranes was investigated. The position distribution and stability of Bacillomycin D in the three different cell membranes were analysed and compared based on density profile calculations. Additionally, we focused on the Radial Distribution Function (RDF) curves between amino acid residues with negative charges or strong hydrophobic properties and the head groups of two different cell membranes. Based on changes in the curvature of the three membranes, the cyclic lipopeptide Bacillomycin D can cause localised surface protrusions in DOPC/DOTAP membranes, inward depressions in the surface of DOPC/DPPA membranes and inhibition deformation in the surface of DOPC membranes. This study will help to further understand the antibacterial mechanism of the cyclic lipopeptide Bacillomycin D and provide a basis for the development of new antibiotics.     

Molecular dynamics simulation of isothermal crystallisation of polymer chains around single polymer lamella

The isothermal crystallisation of polyethylene (PE) chains around single PE lamella in vacuum is investigated by molecular dynamic simulation. The crystallisation process is analysed in terms of the orientational order parameters, principal moments of inertia for the simulated systems. The effects of charge interactions between the polymer chains and lamella are discussed. It is found that the crystallisation process for uncharged systems can be divided into three stages: (1) adsorption, (2) orientation and (3) arrangement. The single polymer lamella changes a little during the three stages. PE chains are arranged parallel to the chain direction of the stems in the crystalline state. When considering the effect of charge interactions between the polymer chains and lamella, a different crystallisation process appears. The single polymer lamella is affected by the charged polymer chains.     

聚合物纳米颗粒对动脉粥样硬化病变的影响及相关机理研究进展

聚合物纳米颗粒通常指基于疏水性聚合物的纳米粒子,由于其良好的生物相容性、高效的长循环特性以及优于其他纳米颗粒物的代谢排出方式等,在纳米医学领域中得到了广泛关注。现有研究证明聚合物纳米颗粒在心血管疾病,尤其是在动脉粥样硬化(atherosclerosis,AS)的诊断、治疗中具有独特的优点,已经成功地由基础研究向临床应用转化。但是聚合物纳米颗粒引起的炎症反应诱导泡沫细胞形成、巨噬细胞自噬,以及心血管系统疾病力学微环境改变引起的聚合物纳米颗粒富集等,都可能最终诱导AS的发生发展。在此,本文综述了近年来聚合物纳米颗粒在诊断、治疗AS疾病中的应用及其与AS病变的关系和机理,为后续研究利用聚合物纳米颗粒开发新型纳米药物治疗AS提供理论依据。     

Interfacial barriers to gas transport: probing solid-gas interfaces at the atomistic level

ABSTRACT

An understanding of interfacial barriers underpinning fluid transport in nanoporous membranes is critical for the design of efficient next generation membranes, to harness their potential for industrial scale separations. Such barriers include the contribution of external and internal interfacial barriers, and strongly depend on smoothness of the pore surface, pore size, shape, tortuosity, structural defects such as pore blockage and thermodynamic state of the fluid. We review recent progress in the transport of a fluid through nanoporous membrane materials such as zeolites and carbon nanotubes, which hold promise for industrial significance, but their application is subject to strong interfacial barriers. The contribution of interfacial barriers to the overall transport in these membrane materials is found to be particularly significant when the pore surface is uniform as well as at low temperatures and pressures. Further, such barriers that arise from internal defects such as grain boundaries are found to be remarkable and detrimental to separation kinetics. The internal interfacial barriers are found to be significant, and are enhanced when a dense medium such as a polymer is present at the interface, suggesting that interfacial barriers can play a key role in mixed matrix membranes and is an important area requiring further attention.     

纳米粒子表面修饰对其与细胞膜相互作用的影响

纳米粒子在生物医学上的应用越来越广泛,其进入细胞的机制与规律是设计与开发的基础．已有研究发现,表面修饰不同亲疏水性基团的金纳米粒子,在内吞机制被抑制时,进入细胞的能力明显不同．更特别的是,粒子表面亲水性基团与疏水性基团呈间隔条纹规则排列的纳米粒子,与其他修饰成分相同仅排列不同的纳米粒子进入细胞的规律区别显著．这一特殊现象无法用已有的纳米粒子进入细胞的机制解释．本文针对该研究结果,将纳米粒子与细胞的体系简化,定量分析了3种不同纳米粒子进入细胞前后的不同状态,计算获得了表面修饰不同亲疏水性基团的纳米粒子与细胞膜之间相互作用的Flory．Huggins自由能．结果发现,修饰规则间隔排列亲疏水基团的纳米粒子,其作用自由能在与细胞接触前后变化最大．研究结果不仅解释了实验发现,同时预示了纳米粒子进入细胞的新机制．     

Tribology of polymer brush: microscale modelling and simulation

In order to examine the tribological behaviour of the polymer brush, we constructed a mesoscale particle model of a polymer brush system, based on a Brownian dynamics scheme. The polymer model consists of coarse-grained beads connected with harmonic springs. The Lennard-Jones type interaction is assumed between beads. The flow velocity is affected by the local packing fraction of beads. With this model, we executed a series of molecular dynamics simulation to investigate the mechanical responses of brush to shear flow.     

Preparation of silver nanoparticles from silver(I) nano-coordination polymer

Nanorods of two-dimensional organometallic coordination polymer, [Ag(μ₄-DPOAc)]_n (1) [DPOAc⁻ = diphenylacetate], has been synthesized by the reaction of potassium diphenylacetate (DPOAcK) and AgNO₃ by sonochemical process. Reaction conditions, such as the concentration of the initial reagents played important roles in the size and growth process of the final product. Silver nanoparticles were synthesized from nanorods of compound 1. These nano-coordination polymer and nanoparticles were characterized by X-ray powder diffraction (XRD) and scanning electron microscopy (SEM). Thermal stability of nano and crystal samples of compound 1 were studied and compared with each other.     

Lipid dynamics and protein-lipid interactions in rat colonic epithelial cell basolateral membranes

Lipid dynamics and lipid-protein interactions were examined in basolateral membranes prepared from rat proximal and distal colonic epithelial cells. The results demonstrate that: (1) these membranes have a high lipid fluidity, as assessed by steady-state fluorescence polarization studies using seven fluorescent probes; (2) lipid compositional differences exist between these membranes but their fluidity is similar; (3) fluorescence polarizations studies, using diphenylhexatriene (DPH), detect a thermotropic transition at 22–23°C in each membrane; (4) several membrane protein activities, including adenylate cyclase and sodium-potassium dependent adenosine triphosphatase ($\text{(}\text{Na}{}^{\mathrm{+}}\text{+}\text{K}{}^{\mathrm{+}}\text{)-}\text{ATPase}$) appear to be functionally dependent on the physical state of the proximal basolateral membrane's lipid.     

Local segmental dynamics of cis-1,4-polybutadiene,polypropylene and polyethylene terephthalate via molecular dynamics simulations

The local segmental dynamics of cis-1,4-polybutadiene, polypropylene and polyethylene terephthalate have been investigated via isothermal-isobaric molecular dynamics simulations. The simulation pressure was 1 atm for all systems, with all simulation temperatures being at least 150 K above the polymer's glass transition temperature. The trajectories have been analysed via autocorrelation functions (ACFs) of chord vectors spanning different number of chain backbone bonds. Inverse Laplace transformations of these ACFs using the CONTIN algorithm afforded the corresponding distribution of relaxation times (DRTs) for the simulated dynamics. All DRTs illustrated a peak on fast timescales corresponding to short length scale segmental motion and a peak at longer timescales corresponding to longer length scale relaxations. A third peak, intermediate between the fast and slow processes, appears as the relaxation of chord vectors spanning increasing number of backbone bonds is considered. The temperature dependence of the relaxation dynamics is also investigated.     

Solution NMR studies of peptide-lipid interactions in model membranes

Abstract

Many important processes in life take place in or around the cell membranes. Lipids have different properties regarding their membrane-forming capacities, their mobility, shape, size and surface charge, and all of these factors influence the way that proteins and peptides interact with the membrane. In order for us to correctly understand these interactions, we need to be able to study all aspects of the interplay between lipids and peptides and proteins. Solution-state NMR offers a somewhat unique possibility to investigate structure, dynamics and location of proteins and peptides in bilayers. This review focuses on solution NMR as a tool for investigating peptide-lipid interaction, and special attention is given to the various membrane mimetics that are used to model the membrane. Examples from the field of cell-penetrating peptides and their lipid interactions will be given. The importance of studying lipid and peptide dynamics, which reflect on the effect that peptides have on bilayers, is highlighted, and in this respect, also the need for realistic membrane models.     

Analysis of cell surface interactions by measurements of lateral mobility

Interactions of cell surface components with one another and with structures inside and outside the cell may have important physiological functions in the transmission of signals and the assembly of specialized structures. These interactions may be detected and analyzed through their effects on the lateral mobility of cell surface molecules. Measurements by a fluorescence photobleaching method have shown that in general lipid-like molecules diffuse rapidly and freely through the plasma membrane, whereas proteins move much more slowly or appear to be immobile. This dichotomy has been supposed to result from forces beyond the viscosity of the lipid bilayer, which specifically retard the diffusion of membrane proteins. This general picture should be qualified, however, by noting that the lateral mobility of lipid-like molecules can be influenced in detail by changes in the state of the plasma membrane such as result from mitosis or fertilization. The interactions of cell surface proteins that limit their lateral mobility are unknown. The effects of binding concanavalin A to localized regions of cell surface show that these interactions can vary in subtle and complex ways. It may soon be useful to interpret mobility experiments in terms of simple reaction models that attempt to describe surface interactions in physicochemical terms. More experimental data are needed to carry out this program and to relate interactions that affect mobility to the structural connections between cell surface components and the cytoskeleton, which have been detected by biochemical methods and electron and immunofluorescence microscopy.     

Probing intercellular interactions between vascular endothelial cadherin pairs at single-molecule resolution and in living cells

Vascular endothelial (VE) cadherin is the surface glycoprotein cadherin specific to the endothelium that mediates cell-cell adhesion and plays a major role in the remodeling, gating, and maturation of vascular vessels. To investigate the contribution of individual VE-cadherins to endothelial cell-cell interactions and investigate whether different classical cadherins display different kinetics and micromechanical properties, we characterize the binding properties of VE-cadherin/VE-cadherin bonds at single-molecule resolution and in living human umbilical vein endothelial cells (HUVECs). Our single-molecule force spectroscopy measurements reveal that type II VE-cadherin molecules form bonds that are less prone to rupture and display a higher tensile strength than bonds formed by classical type I neuronal (N) cadherin and epithelial (E) cadherin. The equilibrium lifetime of the VE-cadherin/VE-cadherin bond is significantly longer than formed by N-cadherin/N-cadherin bonds and E-cadherin/E-cadherin bonds. These results indicate that VE-cadherins form bonds that have kinetics and mechanical properties that are significantly different from those formed by classical type I cadherins, properties that are particularly well adapted to the barrier and adhesive functions of VE-cadherin in endothelial cell-cell junctions.     

CGDB: A database of membrane protein/lipid interactions by coarse-grained molecular dynamics simulations

Membrane protein function and stability has been shown to be dependent on the lipid environment. Recently, we developed a high-throughput computational approach for the prediction of membrane protein/lipid interactions. In the current study, we enhanced this approach with the addition of a new measure of the distortion caused by membrane proteins on a lipid bilayer. This is illustrated by considering the effect of lipid tail length and headgroup charge on the distortion caused by the integral membrane proteins MscS and FLAP, and by the voltage sensing domain from the channel KvAP. Changing the chain length of lipids alters the extent but not the pattern of distortion caused by MscS and FLAP; lipid headgroups distort in order to interact with very similar but not identical regions in these proteins for all bilayer widths investigated. Introducing anionic lipids into a DPPC bilayer containing the KvAP voltage sensor does not affect the extent of bilayer distortion.     

Computer simulation of polymer and biopolymer self-assembly for drug delivery

Molecular simulation is an emerging tool to bridge relevant time- and length-scales in self-assembly and interfacial processes in soft matter and biological systems. In this review, we highlight mesoscale and coarse-grained molecular dynamics simulation techniques as applied to poly(ethylene oxide)-based diblock copolymer self-assembly. Moreover, we review recent progress pertaining to diblock copolymer and biopolymer self-assembly, stability, and finally, interactions of hydrophobic drugs with polymer membranes. We expect that these computational investigations should provide a useful complement to experimental studies that address open questions in the field of polymeric drug delivery.     

Epigallocatechin-3-gallate location and interaction with late endosomal and plasma membrane model membranes by molecular dynamics

Epigallocatechin-3-gallate (EGCG) is the most abundant polyphenol in green tea and it has been reported to have many beneficial properties against many different types of illnesses and infections. However, the exact mechanism/s underlying its biological effects are unknown. It has been previously shown that EGCG is capable of binding to and disrupting the membrane, so that some of its effects on biological systems could be ascribed to its capacity to incorporate into the biological membrane and modulate its structure. In this work, we have used atomistic molecular dynamics (MD) to discern the location and orientation of EGCG in model membranes and the possible existence of specific interactions with membrane lipids. For that goal, we have used in our simulation two complex model membranes, one resembling the plasma membrane (PM) and the other one the late endosome (LE) membrane. Our results support that EGCG tends to associate with the membrane and exists inside it in a relatively stable and steady location with a low propensity to be associated with other EGCG molecules. Interestingly, EGCG forms hydrogen bonds with POPC and POPE in the PM system but POPC and BMP and no POPE in the LE. These data suggest that the broad beneficial effects of EGCG could be mediated, at least in part, through its membranotropic effects and therefore membrane functioning.

Communicated by Ramaswamy H. Sarma     

Study on physisorption between G‐actin and amphiphilic polymer‐coated gold nanoparticles

Physisorptions occurs everywhere and constantly in living organisms and between nanomaterials and biomolecules. In this study, one of the most important proteins, G‐actin, was selected to investigate its bio‐nano physisorption with a model nanoparticle coated with a amphiphilic polymer. Using a photoluminescence quenching method, both the binding constant and the Hill constant were determined as 1.79 × 10⁷ M^?1 and 0.84, respectively. Thermodynamic calculations proved that such a physisorption was a spontaneous procedure. The physisorption‐mediated protein–nanoparticle conjugates were robust enough to resist gel electrophoresis, and protein conformation was kept intact, as revealed using circular dichroism. This conjugate might be a promising candidate for nanofabrication or could play a significant role in actin–related bioactivities.     

Nanopowders of 3D Ag coordination polymer: A new precursor for preparation of silver nanoparticles

Nanopowders of novel three-dimensional Ag^I coordination polymer, [Ag₂(μ₈-SB)]_n (1) [H₂SB = 4-[(4-hydroxyphenyl)sulfonyl]-1-benzenol] has been synthesized by the reaction of SB²⁻ and AgNO₃ by a sonochemical method. Reaction conditions, such as the concentration of the initial reagents and power of the ultrasonic device played important roles in the size, morphology and growth process of the final products. For the first time silver nanoparticles were synthesized from [Ag₂(μ₈-SB)]_n (1) coordination polymer by calcinations and hydrothermal methods. These nanopowders and nanoparticles were characterized by X-ray powder diffraction (XRD), scanning electron microscopy (SEM); transmission electron microscopy (TEM) and energy-dispersive X-ray spectra (EDS). Thermal stability and emission properties of nano and crystal samples of compound 1 were studied and compared with each other.