Marcel Düggelin

Early detection of aging cartilage and osteoarthritis in mice and patient samples using atomic force microscopy

The pathological changes in osteoarthritis--a degenerative joint disease prevalent among older people--start at the molecular scale and spread to the higher levels of the architecture of articular cartilage to cause progressive and irreversible structural and functional damage. At present, there are no treatments to cure or attenuate the degradation of cartilage. Early detection and the ability to monitor the progression of osteoarthritis are therefore important for developing effective therapies. Here, we show that indentation-type atomic force microscopy can monitor age-related morphological and biomechanical changes in the hips of normal and osteoarthritic mice. Early damage in the cartilage of osteoarthritic patients undergoing hip or knee replacements could similarly be detected using this method. Changes due to aging and osteoarthritis are clearly depicted at the nanometre scale well before morphological changes can be observed using current diagnostic methods. Indentation-type atomic force microscopy may potentially be developed into a minimally invasive arthroscopic tool to diagnose the early onset of osteoarthritis in situ.

Influence of iron–silicon interaction on the growth of carbon nanotubes produced by chemical vapor deposition

Carbon nanotubes are often grown by chemical vapor deposition on silicon substrates covered with an iron catalyst. Photoemission and scanning electron microscopy studies presented here reveal how the iron silicide interface phase formed at elevated temperatures influences the catalytic efficiency of the iron. Moreover, we will show how the deposition of a thin layer of dense titanium nitride between the silicon substrate and the iron catalyst effectively prevents the formation of the silicide phase and consequently improves the carbon nanotubes growth.

An Antibody-Sensitized Microfabricated Cantilever for the Growth Detection of Aspergillus niger Spores

We demonstrate a new sensitive biosensor for detection of vital fungal spores of Aspergillus niger. The biosensor is based on silicon microfabricated cantilever arrays operated in dynamic mode. The change in resonance frequency of the sensor is a function of mass binding to the cantilever surface. For specific A. niger spore immobilization on the cantilever, each cantilever was individually coated with anti-Aspergillus niger polyclonal antibodies. We demonstrate the detection of single A. niger spores and their subsequent growth on the functionalized cantilever surface by online measurements of resonance frequency shifts. The new biosensor operating in humid air allows quantitative and qualitative detection of A. niger spores as well as detection of vital, functional spores in situ within approximately 4 h. The detection limit of the sensor is 103 CFU mL-1. Mass sensitivity of the cantilever sensor is approximately 53 pg Hz-1.

Structural and optical properties of titanium aluminum nitride films (Ti1−xAlxN)

Titanium aluminum nitride films (Ti1−xAlxN) have been deposited by reactive magnetron cosputtering. Elemental compositions of these films have been determined by core level photoelectron spectroscopy. Scanning electron microscopy reveals a columnar film growth. This is also reflected by the topography of film surfaces as studied by atomic force microscopy. By x-ray diffraction a crystalline atomic structure is revealed. Single phase samples can be obtained, consisting of the substitutional solid solution (Ti, Al)N. Crystallites show preferential orientation. The optical properties of these films have been investigated by spectrophotometry in the UV-VIS-NIR wavelength range. Depending on the elemental composition, the optical constants vary from metallic to dielectric behavior. For film compositions with x<0.5 typical features are a tunable transmission maximum and reflection minimum in the visible spectral range, a high infrared reflection, and a low infrared absorption. Due to these optical properties, T...

HAARARTIGE HYPERKERATOSEN BEI EINEM NIERENTRANSPLANTIERTEN. EINE NEUE CYCLOSPORIN-NEBENWIRKUNG

ZusammenfassungWir berichten über einen 31jährigen nierentransplantierten Patienten, der unter Cyclosporin A eine ungewöhnliche Talgdrüsenhyperplasie entwickelte, begleitet von einer disseminierten, follikulär gebundenen, spikeartigen Hyperkeratose. Die Hautveränderungen waren besonders ausgeprägt im Gesicht und an den Streckseiten der Extremitäten. Stellenweise imponierte eine haarartige Hyperkeratose mit echter Haarneubildung. Die Histologie dieser Veränderungen zeigte eine stark vermehrte Keratinisation der Haarfollikel mit der Bildung von haarähnlichen „Spikes“, welche teilweise isoliert und in Verbindung mit echten Körperhaaren vorkamen. Aufgrund dieser Eigenschaft lassen sich differentialdiagnostisch die morphologisch sehr ähnliche „Disseminated Spiked Hyperkeratosis“ und andere filiforme Keratosen abgrenzen. Erstmals wird in der vorliegenden Arbeit dieser haarähnliche Aufbau auch mittels rasterelektronenmikroskopischer Aufnahmen dargestellt. Die Talgdrüsenfollikel zeigten eine z.T. zystische Ausweitung, wie sie bereits früher beschrieben worden ist, mit hier ebenfalls stark vermehrter Einlagerung von Keratinmassen. Dieser Fall zeigt, a) daß die beobachteten Hautveränderungen wahrscheinlich der alleinigen Wirkung von Cyclosporin A zuzuordnen und b), daß sie vermutlich dosisabhängig sind.SummaryWe report a 31-year-old renal transplant patient treated with cyclosporin A who developed an unusual sebaceous gland hyperplasia accompanied by a disseminated follicular spiny hyperkeratosis. Those alterations were most evident on his face and limbs. In some locations hairy hyperkeratosis with authentic hair neogenesis was found. The histology of these alterations showed a marked hyperkeratosis of the hair follicles with formation of hair-like spikes either alone or in connection with hairs. The presence of true hairs distinguishes our case from the morphologically similar disseminated spiked hyperkeratosis and other spiny keratinization disorders. Scanning electron microscopy helped to demonstrate the hair-like structure of these keratoses. Some of the sebaceous glands showed cystic widening of their lumina, which were filled with abundant amorphous eosinophilic material, a finding similar to earlier observations. Our case demonstrates that these skin alterations should be classified as side effects of cyclosporin A and that they are apparently dose-dependent.

Preparation and characterization of TiN–Ag nanocomposite films

Abstract Thin nanostructured films of TiN–Ag are deposited by a plasma vapour process consisting of co-sputtering of Ti and Ag from three magnetrons in an Ar–N 2 gas mixture. The coatings are characterized by in situ photoelectron spectroscopy, energy-filtered transmission electron microscopy and scanning electron microscopy. The dependence of the film structure and silver cluster distribution on total silver content, substrate biasing and substrate temperature was investigated.

Mechanical control of mitotic progression in single animal cells

Significance In animal tissue, most adherent cells round up against confinement to conduct mitosis. Impaired cell rounding is thought to perturb tissue development and homeostasis and contribute to progression of cancer. Due to the lack of suitable experimental tools, however, insight into the mechanical robustness of mitosis in animal cells remains limited. Here we introduce force-feedback–controlled ion beam-sculpted cantilevers to confine single cells and characterize their progression through mitosis. Our approach reveals critical yield forces that trigger cell cortex herniation, loss of F-actin homogeneity, dissipation of intracellular pressure, critical cell-height decrease, mitotic spindle defects, and resultant perturbation of mitotic progression. Despite the importance of mitotic cell rounding in tissue development and cell proliferation, there remains a paucity of approaches to investigate the mechanical robustness of cell rounding. Here we introduce ion beam-sculpted microcantilevers that enable precise force-feedback–controlled confinement of single cells while characterizing their progression through mitosis. We identify three force regimes according to the cell response: small forces (∼5 nN) that accelerate mitotic progression, intermediate forces where cells resist confinement (50–100 nN), and yield forces (>100 nN) where a significant decline in cell height impinges on microtubule spindle function, thereby inhibiting mitotic progression. Yield forces are coincident with a nonlinear drop in cell height potentiated by persistent blebbing and loss of cortical F-actin homogeneity. Our results suggest that a buildup of actomyosin-dependent cortical tension and intracellular pressure precedes mechanical failure, or herniation, of the cell cortex at the yield force. Thus, we reveal how the mechanical properties of mitotic cells and their response to external forces are linked to mitotic progression under conditions of mechanical confinement.

Morphological changes of tungsten surfaces by low-flux helium plasma treatment and helium incorporation via magnetron sputtering

The effect of helium on the tungsten microstructure was investigated first by exposure to a radio frequency driven helium plasma with fluxes of the order of 1 × 10(19) m(-2) s(-1) and second by helium incorporation via magnetron sputtering. Roughening of the surface and the creation of pinholes were observed when exposing poly- and nanocrystalline tungsten samples to low-flux plasma. A coating process using an excess of helium besides argon in the process gas mixture leads to a porous thin film and a granular surface structure whereas gas mixture ratios of up to 50% He/Ar (in terms of their partial pressures) lead to a dense structure. The presence of helium in the deposited film was confirmed with glow-discharge optical emission spectroscopy and thermal desorption measurements. Latter revealed that the highest fraction of the embedded helium atoms desorb at approximately 1500 K. Identical plasma treatments at various temperatures showed strongest modifications of the surface at 1500 K, which is attributed to the massive activation of helium singly bond to a single vacancy inside the film. Thus, an efficient way of preparing nanostructured tungsten surfaces and porous tungsten films at low fluxes was found.

Changing TiN film morphology by “plasma biasing”

The influence of the substrate potential with respect to the plasma on the morphology of reactively sputtered TiN thin films on Si(100) has been investigated. It is well known that the film quality with respect to grain size and distribution can be improved by applying a negative substrate bias to increase energetic ion bombardment. For large-area applications, however, a grounded substrate is very much desirable. Therefore, a technique has been developed to deposit films with comparably improved morphology on grounded substrates by means of a so-called “plasma electrode.” Grain size and distribution have been analyzed by top- and side-view scanning electron microscopy. To adjust the parameters for the TiN deposition we have used in situ photoelectron spectroscopy as the process control.

Supramolecular Organization of Collagen Fibrils in Healthy and Osteoarthritic Human Knee and Hip Joint Cartilage.

Cartilage matrix is a composite of discrete, but interacting suprastructures, i.e. cartilage fibers with microfibrillar or network-like aggregates and penetrating extrafibrillar proteoglycan matrix. The biomechanical function of the proteoglycan matrix and the collagen fibers are to absorb compressive and tensional loads, respectively. Here, we are focusing on the suprastructural organization of collagen fibrils and the degradation process of their hierarchical organized fiber architecture studied at high resolution at the authentic location within cartilage. We present electron micrographs of the collagenous cores of such fibers obtained by an improved protocol for scanning electron microscopy (SEM). Articular cartilages are permeated by small prototypic fibrils with a homogeneous diameter of 18 ± 5 nm that can align in their D-periodic pattern and merge into larger fibers by lateral association. Interestingly, these fibers have tissue-specific organizations in cartilage. They are twisted ropes in superficial regions of knee joints or assemble into parallel aligned cable-like structures in deeper regions of knee joint- or throughout hip joints articular cartilage. These novel observations contribute to an improved understanding of collagen fiber biogenesis, function, and homeostasis in hyaline cartilage.