Publikationen

Glucocorticoids (GCs) are widely prescribed therapeutics for the treatment of inflammatory diseases, and endogenous GCs play a key role in immune regulation. Toll-like receptors (TLRs) enable innate immune cells, such as macrophages, to recognize a wide variety of microbial ligands, thereby promoting inflammation. The interaction of GCs with macrophages in the immunosuppressive resolution phase upon prolonged TLR activation is widely unknown. Treatment of human alveolar macrophages (AMs) with the synthetic GC dexamethasone (Dex) did not alter the expression of TLRs -1, -4, and -6. In contrast, TLR2 was upregulated in a GC receptor-dependent manner, as shown by Western blot and qPCR. Furthermore, long-term lipopolysaccharide (LPS) exposure mimicking immunosuppression in the resolution phase of inflammation synergistically increased Dex-mediated TLR2 upregulation. Analyses of publicly available data sets suggested that TLR2 is induced during the resolution phase of inflammatory diseases, i.e., under conditions associated with high endogenous GC production. TLR2 induction did not enhance TLR2 signaling, as indicated by reduced cytokine production after treatment with TLR2 ligands in Dex- and/or LPS-primed AMs. Thus, we hypothesized that the upregulated membrane-bound TLR2 might serve as a precursor for soluble TLR2 (sTLR2), known to antagonize TLR2-dependent cell actions. Supernatants of LPS/Dex-primed macrophages contained sTLR2, as demonstrated by Western blot analysis. Activation of metalloproteinases resulted in enhanced sTLR2 shedding. Additionally, we detected full-length TLR2 and assumed that this might be due to the production of TLR2-containing extracellular vesicles (EVs). EVs from macrophage supernatants were isolated by sequential centrifugation. Both untreated and LPS/Dex-treated cells produced vesicles of various sizes and shapes, as shown by cryo-transmission electron microscopy. These vesicles were identified as the source of full-length TLR2 in macrophage supernatants by Western blot and mass spectrometry. Flow cytometric analysis indicated that TLR2-containing EVs were able to bind the TLR2 ligand Pam3CSK4. In addition, the presence of EVs reduced inflammatory responses in Pam3CSK4-treated endothelial cells and HEK Dual reporter cells, demonstrating that TLR2-EVs can act as decoy receptors. In summary, our data show that sTLR2 and full-length TLR2 are released by macrophages under anti-inflammatory conditions, which may contribute to GC-induced immunosuppression.

Continuous roll-to-roll fabrication is essential for transferring the idea of bio-inspired, fibrillar dry adhesives into large-scale, synthetic, high-performance adhesive tapes. Toward this aim, we investigated process parameters that allow us to control the morphology and the resulting adhesion of mushroom-shaped micropatterned surfaces. Flexible silicone templates enabled the replication process of the polyurethane acrylate pre-polymer involving UV-light-induced cross-linking. For this paper, we particularly tailored the polyurethane acrylate pre-polymer by adding chemical components to tune UV curing kinetics and to reduce oxygen inhibition of radicals. We found that higher intensities of the UV light and faster reaction kinetics improved the quality of the microstructures, i.e., a larger cap diameter of the mushroom tips was achieved. The polymer blend U6E4 exhibited the fastest curing kinetics, which resulted in a micromorphology similar to that of the Ni-shim master structures. Best adhesion results were obtained for adhesive tapes made from U6E4 with 116 kPa pull-off stress, 1.4 N cm−1 peel strength and 71 kPa shear strength. In addition, repeated attachment–detachment tests over 100,000 cycles demonstrated strong robustness and reusability.

Nanotechnologies are characterized by a growing legacy of already marketed and novel manufactured nanomaterials (MNMs) and nano-enabled products with a lack of a coherent risk governance system to address their safety effectively. In response to this situation, a proactive system is needed to minimize the gap between the pace of innovation and the pace of developing nano-specific risk governance. With the Safe Innovation Approach (SIA), we seek to enhance the ability of all stakeholders to address the safety assessment of innovations in a robust yet agile manner. The SIA is an approach that combines a) the Safe-by-Design (SbD) concept, which recommends industry to integrate safety considerations as early as possible into the innovation process, and b) the Regulatory Preparedness (RP) concept which aims to improve anticipation of regulators in order that they can facilitate the development of adaptable (safety) regulation that can keep up with the pace of knowledge generation and innovation of MNMs and MNM-enabled products. SIA promotes a safe and responsible approach for industry when developing innovative products and materials, and stimulates a proactive attitude amongst policymakers and regulators to minimize the time gap between appearance and approval of innovation and appropriate legislation. Here we introduce a SIA framework consisting of creating SIA awareness, developing a SIA methodology (SbD scenarios, SbD methodology including information needs, functionality, and grouping, SIA Toolbox and a nano-specific database), bringing the Trusted Environment and RP concept into an operational level, and the development of novel business for industry and novel governance models for regulators. The SIA framework once implemented will result in a system for MNMs and nano-enabled products that is agile and robust. Current international efforts such as in the OECD are now trying to bring this concept to practice.

Hyperbranched polymers comprised of polyrotaxanes as mechanically stable backbone and grafted polycaprolactone (PCL) side chains are utilized as solid polymer electrolyte for application in lithium metal (LMBs) and lithium ion batteries (LIBs). The polyrotaxanes were obtained from self-assembly of Cyclodextrin (CD) host molecules threading onto polyethylenoxide (PEO) chains. In particular, CD serves as initiator for a ring-opening-polymerization of PCL affording pendant side chains with merely a few monomer unit lengths that foster enhanced lithium ion transport, as mediated by well-defined lamellar morphology of the PCL side chains. An impressive ionic conductivity of 1 mS cm−1 of the solid polymer electrolyte at 60 °C and more than 0.1 mS cm-1 at room temperature in addition to a superior oxidative electrochemical stability of up to 4.7 V vs. Li/Li+ allows for robust galvanostatic cycling in LiFePO4|Li cells, even at reduced temperatures not accessible by commonly utilized PEO-based electrolytes. The hyperbranched polymers can be readily up-scaled and further modified, thereby demonstrating the versatility of the introduced class of solid-state polymer electrolytes, as reflected by its interfacial stability against the high-capacity Lithium metal anode.

Understanding the biorecognition and transduction mechanisms is a key aspect in the development of robust sensing technologies. Therefore, the design of tools and analytical approaches that could allow gaining a deeper insight into the bio- and electrochemical processes would significantly accelerate the progress in the field of biosensors. Herein, we present a novel effective strategy for biosensor design screening based on tandem monitoring of individual system parameters in a droplet. The developed tandem approach couples the simultaneous chronoamperometric characterization of biosensors in the presence of an analyte (glucose) together with dissolved oxygen monitoring using a luminescence-based optical oxygen microsensor. Remarkably, an optical sensor was applied for the first time to analyse the amperometric biosensor response and kinetics. Two types of multi-layer glucose biosensors (first generation) were chosen as a case study and were evaluated at various operating conditions using multi-analytical techniques. Moreover, specific protocols were developed for the detection of oxygen conversion rates, iron and membrane elution inside the multi-layer glucose biosensor system. The presented tandem monitoring approach allows one to identify and build-up the correlations between the critical operation conditions and system parameters affecting the overall biosensor response, its sensitivity and lifetime. Thus, based on the obtained experimental results a more favorable composition of Nafion membrane films and enzyme loadings for glucose biosensors were identified in a time-efficient way and allowed to explain an improved stability (up to 3 months) and linear detection range of glucose concentrations (up to 5 mM). Furthermore, the presented tandem monitoring approach can be readily adapted to other oxygen dependent types of biosensors either for simultaneous multiple substrate detection or as an efficient tool for biosensor design and operating condition screening.

The manufacturing of conventional electroless-based sensors often suffers from mechanical instability leading to irreversible changes in the sensor architecture and morphology resulting in insufficient signal reproducibility and overall degradation of the system. In addition, understanding the transduction mechanisms is a key aspect in the development of crucial sensing technologies. Therefore, the development of tools and analytical approaches that could allow us to gain deeper insight into the operating processes or validation of the design would significantly accelerate the progress in the field of sensors. Herein, we present a novel effective strategy for non-destructive control and validation of sensors consisting of hybrid silicon nanowires deposited with gold nanoparticles (AuNPs/SiNWs) produced via a hydrofluoric acid-assisted electroless fabrication method. To validate the fabrication method and to monitor the deposition rates of hydrofluoric acid-assisted deposition of AuNPs on SiNWs, specific analytical protocols for high resolution inductively coupled plasma mass spectrometry (HR-ICP-MS) and electron microscopy (SEM/TEM) were developed. Moreover, HR-ICP-MS was used for the non-destructive monitoring of the impact of experimental conditions on the quality of the synthesized hybrid nanostructures. Thus, the impact of certain synthesis conditions, viz. acid ratio, deposition time and surface pretreatment, on the deposition rates, morphology and stability of the prepared AuNPs/SiNWs hybrid structures was investigated in detail. The obtained knowledge based on nanoanalytical studies was applied to develop hybrids with a reproducible surface morphology, homogenous AuNPs distribution and stable attachment to the SiNWs surface to be implemented as reliable substrates for surface enhanced Raman scattering (SERS).

Block copolymers are promising materials for electrolytes in lithium metal batteries that can be tuned by changing the individual blocks to independently optimize ion transport as well as electrochemical and mechanical stability. We explored the performance of electrolytes based on modified triblock copolymers poly(isoprene)-block-poly(styrene)-block-poly(ethylene oxide). Large polyethylene oxide (PEO) blocks with a molecular mass of 53 kg mol-1 allowed only for low lithium salt loadings and led to poor ionic conductivity below 60 °C. However, we found that unusually small molecular weight of the ion solvating PEO blocks down to 2 kg mol-1 enabled polymer-in-salt loadings of up to 5:1 Li:EO. A superior total ionic conductivity greater than 1 mS cm-1 was found for optimized compositions above 0 °C with remarkably low temperature dependence in a wide range from -20 °C to 90 °C. We believe that highly ordered 2D lamellae from controlled self-assembly established a beneficial environment for ionic transport with ionic mobility decoupled from segmental polymer motion. This also explains lithium ion transference numbers as high as 0.7 were obtained for the high conductivity samples.

Abstract This work studies the surface facets of gold nanorods (AuNRs) in wet-coated nanoparticle thin films with synchrotron-light-based grazing-incidence wide angle X-ray scattering (GIWAXS), which provides statistically relevant results on many nanoparticles. Air-brush spraying deposits the monodisperse AuNRs into sparse monolayers where the long axis of rods is parallel to the substrate surface. It is found that the crystalline facets of individual AuNRs in the sparse monolayer are all in the same orientation, as indicated by narrow azimuthal widths of (200) reflections, over a macroscopic scale comparable to the substrate. This alignment is probably due to the rods' sitting on high-index surface facets such as (520) and (250). A quantitative analysis of the angles between bulk facets and the surface facets leads to a “nested-octagon” model for the cross sections of AuNRs: shell octagon with high-index crystalline facets (520), (5-20), (2-50), (-2-50), (-5-20), (-520), (-250), and (250), and core octagon consisting of low-index crystalline facets (100), (1-10), (0-10), (-1-10), (-100), (-110), (010), and (110).

Iron is a key transition element in the biosphere and is crucial for living organisms, although its cellular excess can be deleterious. Maintaining the balance of optimal iron availability in the model plant Arabidopsis (Arabidopsis thaliana) requires the precise operation of iron import through the principal iron transporter IRON-REGULATED TRANSPORTER1 (IRT1). Targeted inhibition of IRT1 can prevent oxidative stress, thus promoting plant survival. Here, we report the identification of an IRT1 inhibitor, namely the C2 domain-containing peripheral membrane protein ENHANCED BENDING1 (EHB1). EHB1 interacts with the cytoplasmically exposed variable region of IRT1, and we demonstrate that this interaction is greatly promoted by the presence of calcium. We found that EHB1 binds lipids characteristic of the plasma membrane, and the interaction between EHB1 and plant membranes is calcium-dependent. Molecular simulations showed that EHB1 membrane binding is a two-step process that precedes the interaction between EHB1 and IRT1. Genetic and physiological analyses indicated that EHB1 acts as a negative regulator of iron acquisition. The presence of EHB1 prevented the IRT1-mediated complementation of iron-deficient fet3fet4 yeast (Saccharomyces cerevisiae). Our data suggest that EHB1 acts as a direct inhibitor of IRT1-mediated iron import into the cell. These findings represent a major step in understanding plant iron acquisition, a process that underlies the primary production of bioavailable iron for land ecosystems.

Herein, we introduce an original strategy toward one-step encapsulation, storage and controlled release of low molecular weight organic compounds via electroplated nanoparticles. This concept is demonstrated on the basis of the encapsulation of several organic matrices typically used for matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) as a case study via co-deposition with palladium nanoparticles (Pd-NPs). Remarkably, Pd-NPs act as a capsule for MALDI matrices and thus provide their controlled release depending on the external factors, viz. applied laser fluence or pH of the surrounding media. The proposed approach is considered as a simple, fast and inexpensive preparation method towards the formation of ultimate self-assembled hybrid MALDI matrices with a less pronounced “sweet spot” phenomenon and improved long-term stability.