Scientific publications

Intercellular communication is a fundamental process in the development and functioning of multicellular organisms. Recently, an essentially new type of intercellular communication, based on thin membrane channels between cells, has been reported. These structures, termed intercellular or tunnelling nanotubes (TNTs), permit the direct exchange of various components or signals (e.g., ions, proteins, or organelles) between non-adjacent cells at distances over 100 μm. Our studies revealed the presence of tunnelling nanotubes in microvascular endothelial cells (HMEC-1). The TNTs were studied with live cell imaging, environmental scanning electron microscopy (ESEM), and coherent anti-Stokes Raman scattering spectroscopy (CARS). Tunneling nanotubes showed marked persistence: the TNTs could connect cells over long distances (up to 150 μm) for several hours. Several cellular organelles were present in TNTs, such as lysosomes and mitochondria. Moreover, we could identify lipid droplets as a novel type of cargo in the TNTs. Under angiogenic conditions (VEGF treatment) the number of lipid droplets increased significantly. Arachidonic acid application not only increased the number of lipid droplets but also tripled the extent of TNT formation. Taken together, our results provide the first demonstration of lipid droplets as a cargo of TNTs and thereby open a new field in intercellular communication research.

Ideal cationic polymers for siRNA delivery could result in its enhanced cellular internalization, escape from endosomal degradation, and rapid release in cell cytoplasm, to facilitate knockdown of the target gene. In this study, we have investigated the ability of an in-house synthesized cationic polyrotaxane to bind siRNA into nanometric complexes. This polymer, which had earlier shown improved transfection of model siRNA (luciferase), was used to improve the cellular internalization of the siRNA molecule with therapeutic implications. In cellular assays, the polymer enhanced the knockdown of a gene involved in the pathogenesis of tuberculosis, when the nanocomplexes were compared with free siRNA. The efficacy and cellular non-toxicity of this polymer encourage its further exploitation in animal models of tuberculosis and other intracellular bacterial infections.

Therapeutic gene silencing using small-interfering RNA (siRNA) for treatment of bacterial infections has been neglected in comparison with cancer and viral infections. The aim of our investigation was to formulate siRNA-loaded nanoparticles, using an established cationic polymethacrylate polymer, to enhance the delivery of siRNA into the cytoplasm of macrophages that host many pathogenic bacterial species, including tuberculosis. Nanoparticles of cationic dimethylaminoethyl methacrylate copolymer (Eudragit® E 100) were successfully formulated and were found to efficiently bind the siRNA molecules (Cy3-siRNA, Bfl1/A1 siRNA). The efficiency of nanoparticles in overcoming cellular barriers to intracellular siRNA delivery and the precise pathway of endocytosis of nanoparticles were both confirmed using confocal microscopy. Through efficient siRNA release into the cytoplasm, the siRNA-loaded nanoparticles enabled a five-fold enhancement in the knockdown efficiency of the endogenous host gene Bfl1/A1, when the formulation was compared with free siRNA. Persistence of Bfl1/A1 is useful for phagolysosomal survival of tuberculosis bacteria in macrophages, and the nanoparticles offer a promising concept for exploitation as an anti-tuberculosis therapy.

In recent years, hundreds of scientific studies have been published regarding gecko-inspired adhesives. The primary reason for this increasing interest lies in the unique properties which are combined in the adhesive system of the gecko: this natural system can quickly and repeatedly adhere to different surface chemistry and roughness without the use of adhesion-mediating fluids. Although these properties seem to be inconspicuous at first, there is no man-made system currently available which successfully combines all of these properties and competes with the biological adhesive system. However, there are many applications which may benefit from an artificial adhesion system inspired by geckos, ranging from climbing robots and handling systems to biomedical patches and household objects.

A novel switchable adhesive, inspired by the gecko's fibrillar dry attachment system, is introduced. It consists of a patterned surface with an array of mushroom-shaped pillars having two distinct heights. The different pillar heights allow control of the pull-off force in two steps by application of a low and a high preload. For low preload, only the long pillars form contact, resulting in a low pull-off force. At higher preload, all pillars form contact, resulting in high pull-off force. Even further loading leads to buckling induced detachment of the pillars which corresponds to extremely low pull-off force. To achieve the respective samples a new fabrication method called double inking is developed, to achieve multiple-height pillar structures. The adhesion performance of the two-step switchable adhesive is analysed at varying preload and for different pillar aspect ratios and height relations. Finally, the deformation behavior of the samples is investigated by in situ monitoring.

A switchable dry adhesive based on a nickel–titanium (NiTi) shape-memory alloy with an adhesive silicone rubber surface has been developed. Although several studies investigate micropatterned, bioinspired adhesive surfaces, very few focus on reversible adhesion. The system here is based on the indentation-induced two-way shape-memory effect in NiTi alloys. NiTi is trained by mechanical deformation through indentation and grinding to elicit a temperature-induced switchable topography with protrusions at high temperature and a flat surface at low temperature. The trained surfaces are coated with either a smooth or a patterned adhesive polydimethylsiloxane (PDMS) layer, resulting in a temperature-induced switchable surface, used for dry adhesion. Adhesion tests show that the temperature-induced topographical change of the NiTi influences the adhesive performance of the hybrid system. For samples with a smooth PDMS layer the transition from flat to structured state reduces adhesion by 56%, and for samples with a micropatterned PDMS layer adhesion is switchable by nearly 100%. Both hybrid systems reveal strong reversibility related to the NiTi martensitic phase transformation, allowing repeated switching between an adhesive and a nonadhesive state. These effects have been discussed in terms of reversible changes in contact area and varying tilt angles of the pillars with respect to the substrate surface.

The genetically determined design of structured functional bio/inorganic materials was investigated by applying a convective assembly approach. Wildtype tobacco mosaic virus (wt TMV) as well as several TMV mutants were organized on substrates over macroscopic-length scales. Depending on the virus type, the self-organization behavior showed pronounced differences in the surface arrangement under the same convective assembly conditions. Additionally, under varying assembly parameters, the virus particles generated structures encompassing morphologies emerging from single micrometer long fibers aligned parallel to the triple-contact line through disordered but dense films to smooth and uniform monolayers. Monolayers with diverse packing densities were used as templates to form TMV/ZnO hybrid materials. The semiconducting properties can be directly designed and tuned by the variation of the template architecture which are reflected in the transistor performance.

Medical X-ray imaging requires cost-effective and high-resolution flat-panel detectors for the energy range between 20 and 120 keV. Solution-processed photodetectors provide the opportunity to fabricate detectors with a large active area at low cost. Here, we present a disruptive approach that improves the resolution of such detectors by incorporating terbium-doped gadolinium oxysulfide scintillator particles into an organic photodetector matrix. The X-ray induced light emission from the scintillators is absorbed within hundreds of nanometres, which is negligible compared with the pixel size. Hence, optical crosstalk, a limiting factor in the resolution of scintillator-based X-ray detectors, is minimized. The concept is validated with a 256 × 256 pixel detector with a resolution of 4.75 lp mm−1 at a MTF = 0.2, significantly better than previous stacked scintillator-based flat-panel detectors. We achieved a resolution that proves the feasibility of solution-based detectors in medical applications. Time-resolved electrical characterization showed enhanced charge carrier mobility with increased scintillator filling, which is explained by morphological changes.

A flexible distributed Bragg reflector is made by the infiltration of a nanocolumnar array with polydimethyl siloxane oligomers. The high optical reflectance displayed by the final material is a direct consequence of the high refractive index contrast of the columnar layers whereas the structural stability is due to the polymer properties.

When a nanomaterial enters a biological system, proteins adsorb onto the particle surface and alter the surface properties of nanoparticles, causing drastic changes in physico-chemical properties such as hydrodynamic size, surface charge and aggregation state, thus giving a completely new and undefined physico-chemical identity to the nanoparticles. In the present work, we study the impact of the protein identity (molecular weight and isoelectric point) and the environmental conditions (pH and ionic strength) on the final physico-chemical properties of a model nanoparticle system, i.e. gold nanoparticles. Gold nanoparticles either form stable dispersions or agglomerate spontaneously when mixed with protein solutions, depending on the protein and the experimental conditions. Strikingly, the agglomerates redisperse to individually dispersed and colloidally stable nanoparticles, depending on the purification pH. The final protein coated nanoparticles exhibit specific stabilities and surface charges that depend on protein type and the conditions during its adsorption. By understanding the interactions of nanoparticles with proteins under controlled conditions, we can define the protein corona of the NPs and thus their physico-chemical properties in various media.