Current Nanoscience - Volume 7, Issue 5, 2011

Recent advances in the available experimental techniques to synthesize nanoscale objects (nanoparticles, nanotubes, fullerens, dendrimers) from a variety of starting materials and with a well controlled geometry, size distribution and surface chemistry have opened up new and unprecedented opportunities for using these nanoscale objects for drug delivery, imaging and as antimicrobial agents. The current principal goal is to develop an ability to design nano-objects with programmable functionalities. This requires a fundamental understanding of how nano-objects interact with cell membranes. Gaining this understanding is also important in the context of the potential toxicity of nano-objects and the mechanisms with which they can disrupt the integrity of the cell membrane. Despite a number of recent experimental studies reporting a variety of interaction mechanisms, which depend on the morphology of nano-objects (size, shape), as well as on the characteristics of the environment, the overall picture is incomplete and lacks consistency to offer any concrete design principles. A more systematic description of how nano-objects interact with biological membranes can be constructed with the aid of theoretical modelling and computer simulations. The principle challenge for the conventional atomistic simulations, however, is the characteristic time and length scales of biomolecular processes. For example, engulfing of a nanoparticle by a cell membrane may take microseconds to complete, with profound structural reorganization of the membrane taking place on a length scale of tens and hundreds of nanometers. These time and length scales are not routinely attainable within a typical atomistic-level computer simulation. Furthermore, translocation of a nanoparticle through a cell membrane is a complex process, involving a number of individual steps. These steps occur on very different time and length scales. Thus, to describe this translocation process in its full complexity requires an appropriate multiscale approach that systematically links different scales and levels of the system representation to each other. This special issue of Current Nanoscience is dedicated to the application of multiscale modelling approaches to biomembrane interactions with different types of nano-objects. Nine groups of experts in this field have been invited to present their recent work and share their views on further development and potential applications of the multiscale models. The contributed articles span a wide range of structures with which membranes interact (from structured supports to fullerenes to nanoparticles and nanotubes to proteins), methodologies (coarse-grained models, dissipative particle dynamics, mean field theories) and scales at which the systems are explored. It was a truly rewarding experience to prepare this issue, and I hope the readers of the Current Nanoscience will also find it very useful. I would like to thank Prof. Randy Snurr for suggesting that I put this issue together, and, of course, all the contributors and the reviewers for their diligent effort and timely responses.

We investigate membrane-mediated interactions between transmembrane proteins using coarse-grained models. We compare the effective potential of mean force (PMF) between two proteins, which are always aligned parallel to the z -axis of the simulation box, with those PMFs obtained for proteins with fluctuating orientations. The PMFs are dominated by an oscillatory packing-driven contribution and a smooth attractive hydrophobic mismatch contribution, which vanishes if the hydrophobic length of the protein matches the thickness of the membrane. If protein orientations are allowed to fluctuate, the oscillations are greatly reduced compared to proteins with fixed orientation. Furthermore, the hydrophobic mismatch interaction has a smaller range. Finally, we compare the two-dimensional thickness profiles around two proteins with the predictions from the elastic theory of two coupled monolayers, and find them to be in very good agreement.

Biological applications of fullerenes are severely impeded by our incomplete understanding of their toxicity. Here we extend a recently developed computational method to gain insight into the behavior of fullerenes in lipid bilayer systems. The physical behavior of fullerenes is captured through a continuum model incorporating both their hollow geometry and surface chemistry. By using this model in molecular dynamics simulations we are able to continuously vary the fullerene size and study the resulting variation in equilibrium position, solvation free energy and water to lipid transfer free energy. The results show agreement with all-atom and coarse grained fullerene models and can be extended to study the aggregation of fullerenes in lipid bilayers.

Effects of carbon nanotubes (CNTs) on structural and elastic properties of lipid bilayers are investigated by coarse grained molecular dynamics (CGMD) simulations. The investigations are performed for nanotubes of different lengths and at different nanotube concentrations. The considered structural properties of the bilayers include shapes of their dividing surfaces and lipid tilt and area. It is demonstrated that CNTs embedded in lipid membranes induce long-range perturbations of the membrane shape and lipid tilt. Inhibiting large-wavelength membrane fluctuations (e.g., by confining a system to a small simulation box), leads to a qualitatively different response of the membrane to the CNT-induced perturbations. Elastic properties of the membranes containing CNTs are assessed by measurement of the spectral intensity of the membrane undulations. The spectral intensity increases with addition of nanotubes, which indicates softening of the membrane. This effect becomes more prominent with increasing the CNT length and concentration.

The first step into assessing the nanoparticle (NP) cytotoxicity requires a thorough understanding of the NP-membrane interaction mechanism. The main aim of this study is to investigate the relationship of the surface hydrophobicity distribution of the NP with its translocation efficiency. Two types of NPs, one with a random and one with a striped hydrophobic-hydrophilic surface pattern, are investigated using Molecular Dynamics (MD) simulations and free-energy calculations. The MARTINI coarse-grained description is employed. The results illustrate the significance of the NP surface chemistry pattern by revealing that an ordered distribution of surface hydrophilic groups gives rise to generically different behavior to that of a NP with randomly placed surface hydrophilic groups. The stripedpatterned NP prefers to adopt an interfacial positioning on the membrane, whereas the random-patterned NP gets ‘ trapped’ within the lipid bilayer. From an inverse engineering point of view, the present study provides insight into the surface design of NPs with tailored functionalities, such as direct cellular entry and maximization of cellular uptake.

Via Dissipative Particle Dynamics (DPD) approach, we study the spontaneous insertion of amphiphilic nanotubes into a lipid vesicle, which is immersed in a hydrophilic solvent. Individual lipids are composed of a hydrophilic head group and two hydrophobic tails. Each nanotube encompasses an ABA architecture, with a hydrophobic shaft (B) and two hydrophilic ends (A). To facilitate the selective transport of species through the nanotubes, we introduce hydrophilic tethers at one end of the tube. We show that nanotubes initially located in the host solvent spontaneously penetrate the vesicle's membrane and assume a transmembrane position, with the hydrophilic tethers extending from the surface of the vesicle. Adding nanotubes one at a time after the previous nanotube has been inserted, we characterize the interactions among the nanotubes that have self-assembled into the vesicle's membrane and focus on their clustering within the membrane. We also show that the nanotube insertion and clustering within the vesicle strongly affects the vesicle shape in cases of a sufficiently large number of tubes. Ultimately, these nanotube-lipid systems can be used for creating hybrid controlled release vesicles.

We present mesoscale molecular modeling of lipid bilayer systems supported on a variety of patterned substrates. The model can easily be tuned between regimes dominated by adsorption to the substrate or dominated by line tension between phase separated systems. We show that we can generate arbitrary shapes relevant for bio-nanotechnology and study computationally experimentally relevant systems to a high degree of detail. Especially, properties like membrane stress distributions which cannot experimentally be accessed allow a high degree of understanding of these systems.

Certain membrane proteins, peptides, nanoparticles and nanotubes have rigid structure and fixed shape. They are often viewed as spheres and cylinders with certain surface properties. Single Chain Mean Field theory is used to model the equilibrium insertion of nanoscale spheres and rods into the phospholipid bilayer. The equilibrium structures and the resulting free energies of the nano-objects in the bilayer allow to distinguish different orientations in the bilayer and estimate the energy barrier of insertion.

Targeted drug delivery using functionalized nanocarriers (NCs) is a strategy in therapeutic and diagnostic applications. In this paper we review the recent development of models at multiple length and time scales and their applications to targeting of antibody functionalized nanocarriers to antigens (receptors) on the endothelial cell (EC) surface. Our mesoscale (100 nm-1 µ m) model is based on phenomenological interaction potentials for receptor-ligand interactions, receptor-flexure and resistance offered by glycocalyx. All free parameters are either directly determined from independent biophysical and cell biology experiments or estimated using molecular dynamics simulations. We employ a Metropolis Monte Carlo (MC) strategy in conjunction with the weighted histogram analysis method (WHAM) to compute the free energy landscape (potential of mean force or PMF) associated with the multivalent antigen-antibody interactions mediating the NC binding to EC. The binding affinities (association constants) are then derived from the PMF by computing absolute binding free energy of binding of NC to EC, taking into account the relevant translational and rotational entropy losses of NC and the receptors. We validate our model predictions by comparing the computed binding affinities and PMF to a wide range of experimental measurements, including in vitro cell culture, in vivo endothelial targeting, atomic force microscopy (AFM), and flow chamber experiments. The model predictions agree quantitatively with all types experimental measurements. On this basis, we conclude that our computational protocol represents a quantitative and predictive approach for model driven design and optimization of functionalized NCs in targeted vascular drug delivery.

We present a multiscale approach to the modeling and simulation of human skin with an emphasis on dermal drug delivery. We focus on the top-layer of the skin, the stratum corneum, which is modeled at three distinct resolutions covering macroscopic, mesoscopic and microscopic levels. At the macroscale the stratum corneum is represented as a two-phase composite model of impermeable corneocyte cells embedded in a permeable lipid matrix. We calculate the permeability of a test compound as a function of cell thickness and show how this may be influenced by changes in local humidity. We find that increasing humidity leads to an increase in diffusion normal to the skin surface, but a decrease in overall permeability due to the increase in path length. At the mesoscale we zoom in on the extracellular space at a resolution of about 1 nm and model a mixture of lipids in confinement using an assembly of coarse-grained particles. The self-assembled morphology is predicted as a function of the composition of the lipid phase, by varying the relative amount of ceramides, free fatty acids, and cholesterol. Mixtures of ceramide type 2 and palmitic acid are found to readily separate into lamellae. After phase separation we study diffusion of test probes, where increased diffusivity correlates with drug molecules with increased lipophilicity (log P). At the microscale we focus on the ceramide lipid multilayer. We simulate the molecular dynamics of a TeCd quantum dot inside a ceramide bilayer at constant temperature and pressure. The presence of a nanoparticle has the effect of decreasing the lipid chain radius of gyration and minor alterations in the hydrogen bonding pattern, stabilizing the layer.

β-cyclodextrin based Batch, Flow-Through and “Teabag” Prototype Molecular Reactors have been assembled and used in variety of conventional synthetically useful free radical transformations (Hydrogen Transfer Reactions, Radical Cascade Reactions and Mn(OAc)3 mediated cascade/oxidation reactions. Reactions proceeded smoothly in all cases in good to excellent yields at ambient temperature in aqueous and organic media. The advantages of newly assembled setup are ease of setup, recyclability of the β-cyclodextrin media, flexibility and scope of the transformations to be performed and ease of scale-up of methodology.

In this research, we present the synthesis and the characterization of two novel amphiphilic copolymers based on a pegylated α,β-poly(N-2-hydroxyethyl)-D,L-aspartamide (PHEA) backbone linked to squalene-derived chains bearing 17 or 27 carbon atoms (SqCHO C17 or SqCHO C27). These copolymers were obtained starting from PHEA-poly(ethylene glycol) derivative (PHEA-PEG2000), which was functionalized with ethylenediamine (EDA) and then with SqCHO C17 or SqCHO C27, to obtain PHEA-PEG2000-EDA-SqC17 and PHEA-PEG2000-EDA-SqC27 copolymers, respectively. 1H-NMR and size exclusion chromatography (SEC) analyses confirmed the occurrence of derivatization. Polymeric micelles from both copolymers were obtained by using the dialysis method and were characterized in terms of mean size, zeta potential and critical aggregation concentration (CAC). Furthermore, the formation of micellar nanosystems was confirmed by TEM analysis. These micelles were stable in physiological conditions; in vitro experiments showed that these systems had no cytotoxic effects on Caco-2 and Neuro2a cell lines and no haemolytic activity. Moreover, both PHEA-PEG2000-EDASqC17 and PHEA-PEG2000-EDA-SqC27 micelles were able to penetrate into Neuro2a and Caco-2 cells and to escape from phagocytosis by the J774 A.1 macrophages.

Morphological, structural and chemical evolution in Ti/B/H2 system is studied in detail as a function of mechanical treatment. Ti/B powder continuously changes both in composition and morphology during ball-milling in H2 flow: The powder composition varies from Ti/B to TiH2-x/B causing a change in mechanical properties. The role of boron additive also changes from preventing the Ti nanoparticles from sticking together in the early stages to a matrix material participating in Ti - B interface reactions in the intermediate and final stages of the process. Boron atoms participating in the formation of nanoscopic holes give rise to new H states in the hydride by changing the local atomic state of Ti atoms. The dynamics of the formation of these sites and the redistribution of hydrogen between different types of occupation sites in dependence of phase composition and milling time of the powders are also studied.

We report a simple, low cost and eco-friendly synthesis of Cu2O nanoparticles by reduction of Fehling's solution using Manihot esculenta leaf extract containing reducing sugars which act as reducing agent. The purification process of the Cu2O product does not require expensive methods, since a solid product is obtained from a reaction in liquid phase. The result indicates that aldehyde group present in reducing sugars plays excellent role in the formation of cuprous oxide nanoparticles in the solution. The antibacterial properties of Cu2O nanoparticles were investigated against Escherichia coli as a model for Gram-negative bacteria. Bacteriological tests were performed in solid agar plates and in liquid systems supplemented with different concentrations of nano sized Cu2O nanoparticles. These particles were shown to be an effective bactericide. The resulting Cu2O nanoparticles were characterized by UV-VIS absorption spectroscopy, Fourier-transform infrared (FTIR) spectroscopy, X-Ray Diffraction (XRD) and Scanning Electron Microscopy (SEM).

Nanocrystalline hydroxyapatite (nHA) of 50 nm average diameter and length to diameter ratio of > 3 was synthesized by biomimetic method. Non-isothermal sintering improved densification behavior and mechanical properties of apatite to 0.88 maximum fractional density, 70MPa bending strength, 148MPa compressive strength and 2.53GPa microhardness at sintering temperature of 1250° C. Higher sintering temperatures resulted in the decomposition of the apatite and in-situ biphasic calcium phosphate HAP/TCP formation. This process lowered apatite densification and weakened mechanical properties of the sintered specimen. Transmission electron microscopy (TEM), x-ray diffraction (XRD) and field emission scanning electron microscopy (FESEM) helped to elucidate the structure/property correlations.

Vanadium oxide-based composite catalysts were prepared, and their activities in a styrene oxidation reaction were tested. These catalysts included (i) vanadium oxide (VxOy) supported on multi-walled carbon nanotubes (CNTs) (CNTs-VxOy), (ii) a carbon nanotube CNTs-VxOy template coated with γ-Al2O3 (CNTs-VxOy/Al2O3), (iii) γ-Al2O3/VxOy nanoparticles and (iv) vanadium oxide nanotubes (VxOy-NTs). The structure of these catalysts was determined by TEM, SEM, nitrogen adsorption (BET surface area), TGA and FTIR. The oxidation process was examined between styrene and anhydrous hydrogen peroxide which was catalyzed using the above VxOy-based composite catalyst. The vanadium particles embedded on the wall of CNTs have a satisfactory catalytic activity for oxidation. The effect of the operating parameters, including the reaction temperature, solvent type, reaction time, oxidant concentration and catalyst loading, on styrene conversion and benzaldehyde selectivity was studied.

A random two-dimension electronic conduction nano-network of MWCNTs is fabricated by N ion beam irradiation. The CNTs networks were fabricated by the coalescence of MWCNTs at the crossing and the parallel positions. An increase in electrical conductivity of CNT network was observed by a factor of 1.44 after it was subjected to ion beam irradiation. The increased electrical conductivity resulted from increased inter-CNT transport of charge carriers, with the cross-links acting as bridges between successive CNTs. This phenomenon of increased electronic conduction resulting from coalescence through N ion beam irradiation is discussed.

Carbon nanotubes (CNTs) were produced by arc method and effect of magnetic field on the purity of carbon nanotubes was investigated. In order to control arc discharging, a magnetic field was applied around the arc plasma. The samples were characterized by SEM, XRD and Raman spectroscopy measurements. The SEM images showed, the CNTs produced in the presence of magnetic field have much more purity and regularity than those produced in the absence of magnetic field. The results were confirmed by reduction of D Raman active mode intensity which is an indication of impurities in the CNTs.

NGR-peptide-conjugated polymeric liposome, NGR/liposome/PEI/ODN (NGR/LPD), was prepared with oligodeoxynucleotide (ODN) condensed with PEI at a N/P ratio of 10:1 and PEG-stabilized liposome composed of 94% POPC, 2% DDAB, 3% DSPEPEG- 2000 and 1% DSPE-PEG-2000-maleimide. Liposome/PEI/ODN (LPD) complexes could significantly reduce toxicity of PEI and also enhance uptake of ODN by MCF-7 breast cancer cells compared with naked ODN. It was found that the differences in apoptosis index between NGR/LPD and LPD group were significant (P< 0.05). Tumor tissue showed necrosis in high dose group of NGR/LPD (20 µ g ASODN). In comparison with control group, the levels of hTERT mRNA, hTERT protein as well as c-Myc protein in the NGR/LPD group were markedly lower (P<0.05) and the level of Bcl-2 protein in the NGR/LPD group was significantly higher (P<0.05). NGR/LPD had the function of targeting to tumor cells compared with LPD and could inhibit tumor cells growth compared with control group.

Znic oxide nano- and submicro-structures have been synthesized controllably by the polymeric precursor method (Pechini). In this approach, zinc acetate Zn(CH3COO)2.2H2O, citric acid and ethylene glycol were used as the source of Zn2+, the chelating agent and the connecting agent, respectively. The microstructure of the ZnO nano- and submicro-structures was characterized by X-ray diffractometry (XRD) and scanning electron microscopy (SEM) with the energy dispersive X-ray spectroscopy (EDX), transmission electron microscopy (TEM), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FT-IR). The effect of ethylene glycol to citric acid mole ratio on the morphology and structure of the products was discussed. Different morphologies such as nanoparticles, circular and hexagonal submicro-rods was achieved by changing EG:CA mole ratio. The ZnO nano- and submicro-rods was obtained with EG:CA mole ratio equal to 4:1.The optical property was investigated by the room temperature photoluminescence (PL) spectra. Rod-like and spherical ZnO nanostructures show strong UV emission but hexagonal ZnO submicro-rods show both UV (at ˜ 384 nm) and green emission (at ˜ 510 nm) are observed in the PL spectra.

Ag nanofluids with different concentration (0.03˜ 0.12vol%) were prepared by dispersing chain-like Ag clusters into ethylene glycol. The thermal conductivity and rheological behaviors of the Ag nanofluids were investigated at temperatures ranging from room temperature (15.8 °C) to 65 °C. The results show that the Ag nanofluids is Newtonian flow. The relative viscosity of the Ag nanofluids increases with the raise of particle volume fraction and is independent of temperature. The effective thermal conductivity of the Ag nanofluids increases with the particle volume fraction and temperature. It implies that the Ag nanofluids are better than the base fluid as heat transfer fluids especially in high temperature conditions. The viscosity and effective thermal conductivities of the Ag nanofluids can not be predicted by present models, and more work is needed to be done in the future.

In this work, the Fe3O4 magnetic nanoparticles with different shapes and average sizes of 15 to 180 nm were synthesized by an electrooxidation method, the size and shape of the particles were experimentally controlled by tuning the parameters of potential and electrolyte temperature, and its structure was conducted by XRD, forming the Fe3O4 phase. FT-IR confirmed that the stabilizer molecules can cover the particle surfaces. The resultant TEM and SEM showed that the particles have polycrystalline structure, and their size, shapes and surface morphology change dramatically under different potentials and temperatures. Also the particle size dependency was obtained by using UV-Vis spectroscopy, indicating that their maximum absorption wavelength and peak width decrease with increasing temperature and potential.

The Physic Nut seed oil extracted by screw pressing was assayed for free radical scavenging activity by DPPH and tyrosinase inhibition activity by the dopachrome methods. The oils gave both activities similar to vitamin C. The maximum loading of the oil in niosomes composed of Tween 61/cholesterol at 3:7 molar ratio prepared by chloroform film method with sonication was 1%w/v. The niosomes were stable at 28°C for 8 weeks with an average size determined by dynamic light scattering (DLS) of about 120 nm. The oil entrapped in niosomes gave higher scavenging and tyrosinase inhibition activity than the unentrapped oil of about 3-5 and 1-2 times (p < 0.1), respectively. This study has indicated the potential enhancement of free radical scavenging activity and tyrosinase inhibition activity of Physic Nut oil by entrapping in niosomes.

The two important controllable parameters in the dip-pen nanolithography (DPN) process, such as writing temperature and velocity, are used to investigate the related effects on mechanisms of transference of alkanethiol self-assembled monolayer (SAM), transfer number, gasification number, and nanowire formation using molecular dynamics simulations. The simulated results show that the molecular transport ability during the direct-write process from the tip to the substrate is dependent on writing temperature and velocity, because the molecules have high kinetic energy and undergo fast diffusion when the temperature is increased; high transfer ability occurs at a slow writing velocity. The nanowire thickness and length increase significantly with increasing writing temperature, and its length increases much faster than its thickness (height). When the writing temperature is increased, transfer number and gasification number of the molecules become dramatically larger. The transfer number of ink molecules increases with decreasing writing velocity.