Scientific publications

Little is known about the simultaneous uptake of different engineered nanoparticle types, as it can be expected in our daily life. In order to test such co-exposure effects, murine macrophages (J774A.1 cell line) were incubated with gold (AuNPs) and iron oxide nanoparticles (FeOxNPs) either alone or combined. Environmental scanning electron microscopy revealed that single NPs of both types bound within minutes on the cell surface but with a distinctive difference between FeOxNPs and AuNPs. Uptake analysis studies based on laser scanning microscopy, transmission electron microscopy, and inductively coupled plasma optical emission spectrometry revealed intracellular appearance of both NP types in all exposure scenarios and a time-dependent increase. This increase was higher for both AuNPs and FeOxNPs during co-exposure. Cells treated with endocytotic inhibitors recovered after co-exposure, which additionally hinted that two uptake mechanisms are involved. Cross-talk between uptake pathways is relevant for toxicological studies: Co-exposure acts as an uptake accelerant. If the goal is to maximize the cellular uptake, e.g., for the delivery of pharmaceutical agents, this can be beneficial. However, co-exposure should also be taken into account in the case of risk assessment of occupational settings. The demonstration of co-exposure-invoked pathway interactions reveals that synergetic nanoparticle effects, either positive or negative, must be considered for nanotechnology and nanomedicine in particular to develop to its full potential.

Liquid-phase transmission electron microscopy (TEM) is used for in-situ imaging of nanoscale processes taking place in liquid, such as the evolution of nanoparticles during synthesis or structural changes of nanomaterials in liquid environment. Here, it is shown that the focused electron beam of scanning TEM (STEM) brings about the dissolution of silica nanoparticles in water by a gradual reduction of their sizes, and that silica redeposites at the sides of the nanoparticles in the scanning direction of the electron beam, such that elongated nanoparticles are formed. Nanoparticles with an elongation in a different direction are obtained simply by changing the scan direction. Material is expelled from the center of the nanoparticles at higher electron dose, leading to the formation of doughnut-shaped objects. Nanoparticles assembled in an aggregate gradually fuse, and the electron beam exposed section of the aggregate reduces in size and is elongated. Under TEM conditions with a stationary electron beam, the nanoparticles dissolve but do not elongate. The observed phenomena are important to consider when conducting liquid-phase STEM experiments on silica-based materials and may find future application for controlled anisotropic manipulation of the size and the shape of nanoparticles in liquid.

Self-assembled monolayers introduce chemical functionalities to material surfaces, providing a route to tune their equilibrium and dynamical properties. We report on atomic force microscopy measurements and simulations of adhesion and friction forces caused by a macromolecular host–guest system, where the host molecules are attached to silicon oxide surfaces by means of self-assembled silane layers. Different preparation routes for the silane layers lead to different flexibility of the molecular attachment. The velocity dependencies of the work of separation and of friction vary significantly for attachments with different flexibility. Stiff attachment leads to low pull-off forces at low pulling velocity and to vanishing friction forces in the limit of low sliding velocity. Flexible attachment enhances cooperative contribution of multiple molecular bonds to adhesion and friction and causes significant friction at low sliding velocity. The latter observation can be explained by the contribution of intermittent contact aging to the friction force.

In single-molecule force spectroscopy, the unbinding force is often used to quantify the interaction strength of single molecular bonds. We analyze force spectroscopy of fast reversible bonds probed in thermodynamic equilibrium by considering the dynamics of force probe and molecular linker. The effect of cantilever and linker dynamics is systematically addressed by measuring the unbinding force of single cyclodextrin inclusion complexes by atomic force spectroscopy for a variety of molecular linkers and varying force probe stiffness. The unbinding force of individual bonds probed in thermodynamic equilibrium is not unique for the molecular system but scales with , the square root of the force probe stiffness, and is largely independent of the molecular linker stiffness. The observations are explained by an effective potential resulting from fast linker fluctuations and fast rebinding kinetics which is probed by an AFM cantilever. The slow cantilever dynamics in the kHz range act as mechanical low pass filter, allowing for fast rebinding kinetics of the molecular complex in the order of 106 kHz. The binding energy of the complex can be estimated from the unbinding force as a function of cantilever stiffness, however with some uncertainty arising from lack of a model in three dimensions.

The nanoscale lubrication properties of graphene depend on chemical functionalization, adsorbants, and bonding to the substrate. The dependence of friction on the rotational orientation of graphene on a Pt(111) surface was studied by high-resolution friction force microscopy in ultra-high vacuum and interpreted through complementary simulations. Lateral forces reveal an atomic-scale stick-slip motion with the periodicity of the graphene structure. Additionally, the lateral forces were modulated by a Moiré pattern, which depends on the rotation of the respective domain. Comparing the experimental results to simulations of the friction process based on the Prandtl-Tomlinson model and to atomistic simulations of the tip-sample interactions, it was found that the modulation of lateral forces originated from a structural mismatch between Pt(111) and graphene domains that were locally pinned to the substrate. Domains with preferred orientations, such as the R1° and the R24°, appeared to exhibit lower average friction than those with orientations less frequently observed, such as the R10° domain.

Thermally grown surface oxide layers dominate the single-asperity tribological behavior of a Zr60Cu30Al10 glass. Increase in oxidation time leads to an increased contribution of shearing and a corresponding decreased contribution of ploughing to friction. This change in the dominating friction and wear mechanism results in an overall minor decrease of the friction coefficient of oxidized surfaces compared to the metallic glass sample with native surface oxide. Our results demonstrate the importance of creating a stable oxide layer for practical applications of metallic glasses in micro-devices involving sliding contact.

The confinement of liquids in nanometer-scale gaps can lead to changes in their viscous shear properties. For liquids of polar molecules, the charge state of the confining surfaces has a significant influence on the structure in the confined liquid. Here we report on the implementation of dynamic shear force microscopy in an electrochemical cell. Lateral oscillations of the tip of an atomic force microscope were magnetically activated at a frequency of about 50 kHz. The damping of the lateral tip oscillation was recorded as a function of the tip-sample distance and of the electrode potential at the surface of a Au(100) single crystal electrode. The influence of surface charges on the shear response of the nano-confined liquids was demonstrated for the ionic liquid [EMIM][NTf2] and for aqueous Na2SO4 solution.

Nanotechnology is showing promise in many medical applications such as drug delivery and hyperthermia. Nanoparticles administered to the respiratory tract cause local reactions and cross the blood–air barrier, thereby providing a means for easy systemic administration but also a potential source of toxicity. Little is known about how these effects are influenced by preexisting airway diseases such as asthma. Here, BALB/c mice are treated according to the ovalbumin (OVA) asthma protocol to promote allergic airway inflammation. Dispersions of polyethylene-glycol-coated (PEGylated) and citrate/tannic-acid-coated (citrated) 5 nm gold nanoparticles are applied intranasally to asthma and control groups, and (i) airway resistance and (ii) local tissue effects are measured as primary endpoints. Further, nanoparticle uptake into extrapulmonary organs is quantified by inductively coupled plasma mass spectrometry. The asthmatic precondition increases nanoparticle uptake. Moreover, systemic uptake is higher for PEGylated gold nanoparticles compared to citrated nanoparticles. Nanoparticles inhibit both inflammatory infiltrates and airway hyperreactivity, especially citrated gold nanoparticles. Although the antiinflammatory effects of gold nanoparticles might be of therapeutic benefit, systemic uptake and consequent adverse effects must be considered when designing and testing nanoparticle-based asthma therapies.

In this study, a novel approach for preparation of green fluorescent protein (GFP)-doped silica nanoparticles with a narrow size distribution is presented. GFP was chosen as a model protein due to its autofluorescence. Protein-doped nanoparticles have a high application potential in the field of intracellular protein delivery. In addition, fluorescently labelled particles can be used for bioimaging. The size of these protein-doped nanoparticles was adjusted from 15 to 35 nm using a multistep synthesis process, comprising the particle core synthesis followed by shell regrowth steps. GFP was selectively incorporated into the silica matrix of either the core or the shell or both by a one-pot reaction. The obtained nanoparticles were characterised by determination of particle size, hydrodynamic diameter, ζ-potential, fluorescence and quantum yield. The measurements showed that the fluorescence of GFP was maintained during particle synthesis. Cellular uptake experiments demonstrated that the GFP-doped nanoparticles can be used as stable and effective fluorescent probes. The study reveals the potential of the chosen approach for incorporation of functional biological macromolecules into silica nanoparticles, which opens novel application fields like intracellular protein delivery.

In recent years, fluorescent nanomaterials have gained high relevance in biological applications as probes for various fluorescence-based spectroscopy and imaging techniques. Among these materials, dye-doped silica nanoparticles have demonstrated a high potential to overcome the limitations presented by conventional organic dyes such as high photobleaching, low stability and limited fluorescence intensity. In the present work we describe an effective approach for the preparation of fluorescent silica nanoparticles in the size range between 15 and 80 nm based on L-arginine-controlled hydrolysis of tetraethoxysilane in a biphasic cyclohexane–water system. Commercially available far-red fluorescent dyes (Atto647N, Abberior STAR 635, Dy-647, Dy-648 and Dy-649) were embedded covalently into the particle matrix, which was achieved by aminosilane coupling. The physical particle attributes (particle size, dispersion, degree of agglomeration and stability) and the fluorescence properties of the obtained particles were compared to particles from commonly known synthesis methods. As a result, the spectroscopic characteristics of the presented monodisperse dye-doped silica nanoparticles were similar to those of the free uncoupled dyes, but indicate a much higher photostability and brightness. As revealed by dynamic light scattering and ζ-potential measurements, all particle suspensions were stable in water and cell culture medium. In addition, uptake studies on A549 cells were performed, using confocal and stimulated emission depletion (STED) microscopy. Our approach allows for a step-by-step formation of dye-doped silica nanoparticles in the form of dye-incorporated spheres, which can be used as versatile fluorescent probes in confocal and STED imaging.