INMdok (Leibniz Institute for New Materials)
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Inhibition of Collagenase Q1 of Bacillus cereus as a Novel Antivirulence Strategy for the Treatment of Skin-Wound Infections
Get PDFAbstract Despite the progress in surgical techniques and antibiotic prophylaxis, opportunistic wound infections with Bacillus cereus remain a public health problem. Secreted toxins are one of the main factors contributing to B. cereus pathogenicity. A promising strategy to treat such infections is to target these toxins and not the bacteria. Although the exoenzymes produced by B. cereus are thoroughly investigated, little is known about the role of B. cereus collagenases in wound infections. In this report, the collagenolytic activity of secreted collagenases (Col) is characterized in the B. cereus culture supernatant (csn) and its isolated recombinantly produced ColQ1 is characterized. The data reveals that ColQ1 causes damage on dermal collagen (COL). This results in gaps in the tissue, which might facilitate the spread of bacteria. The importance of B. cereus collagenases is also demonstrated in disease promotion using two inhibitors. Compound 2 shows high efficacy in peptidolytic, gelatinolytic, and COL degradation assays. It also preserves the fibrillar COLs in skin tissue challenged with ColQ1, as well as the viability of skin cells treated with B. cereus csn. A Galleria mellonella model highlights the significance of collagenase inhibition in vivo
Unspecific CTL Killing Is Enhanced by High Glucose via TNF-Related Apoptosis-Inducing Ligand
Get PDFTNF-related apoptosis inducing ligand (TRAIL) is expressed on cytotoxic T lymphocytes (CTLs) and TRAIL is linked to progression of diabetes. However, the impact of high glucose on TRAIL expression and its related killing function in CTLs still remains largely elusive. Here, we report that TRAIL is substantially up-regulated in CTLs in environments with high glucose (HG) both in vitro and in vivo. Non-mitochondrial reactive oxygen species, NFκB and PI3K/Akt are essential in HG-induced TRAIL upregulation in CTLs. TRAILhigh CTLs induce apoptosis of pancreatic beta cell line 1.4E7. Treatment with metformin and vitamin D reduces HG-enhanced expression of TRAIL in CTLs and coherently protects 1.4E7 cells from TRAIL-mediated apoptosis. Our work suggests that HG-induced TRAILhigh CTLs might contribute to the destruction of pancreatic beta cells in a hyperglycemia condition
Perception of friction in tactile exploration of micro-structured rubber samples
Get PDFFingertip friction and the related shear of skin are key mechanical mechanisms in tactile perception, but the perception of friction itself is rarely explored except for the flat surfaces of tactile displays. We investigated the perception of friction for tactile exploaration of a unique set of samples whose fabric-like surfaces are equpped with regular arrays of flexible micropillars.The measured fingertip friction increases with decreasing bending stiffness, where the latter is controlled by radius (20-75 µm) an aspect ration of the micropillars. In forced-choice tasks, participants noticed relative differences in friction as small as 0.2, and even smaller when a sample with less than 100µm distance between pillars is omitted from the analysis. In an affective ranking of sample upon active touch, the perception of pleasantness is anticorrelated with the measured friction. Our results offer insights towards a rational design of materials with well-controlled surface microstructure which elicit a dedicated tactile appeal
Soft Electronics by Inkjet Printing Metal Inks on Porous Substrates
Get PDFSoft electronic devices enable new types of products for an ergonomic interaction of humans with a digital environment. The inkjet (droplet on demand) printing of electrically conductive ink on soft substrates such as paper, textile, and polymers is a promising route for the prototyping and small-scale production of soft electronics that is efficient, cost-saving, and provides a rapid turnaround due to its fully digital workflow. The choice of materials and processing parameters is challenging, however, due to the combined complexity of metal-containing inks, their dynamics during droplet ejection, the active role of the porous substrate, and possible post-deposition steps. This review focuses on recent developments in inkjet printing of metal inks onto soft, porous substrates and their applications. The first section discusses the general principles in the inkjet printing of metal inks, including drop formation and jetting, wetting, and post treatment processes. The second section deals with the effect that the porosity of substrates has on the drying, diffusion, and adhesion of inks. Finally, current challenges and achievements of inkjet-printed, metal-containing inks are discussed
Mechanochemical Ionization: Differentiating Pressure-, Shear-, and Temperature-Induced Reactions in a Model Phosphate
Get PDFUsing density-functional theory-based molecular dynamics simulations, we study stress and temperature-induced chemical reactions in bulk systems containing triphosphoric acid and zinc phosphate molecules. The nature of the products depends sensitively on the imposed conditions, e.g., isotropic and even more so shear stress create (zwitter-) ionic products. Free ions also emerge from thermal cycles, but the reactions are endothermic rather than exothermic as for stress-induced transitions and zinc atoms remain four-coordinated. Hydrostatic stresses required for reactions to occur lie well below those typical for tribological micro-contacts of stiff solids and are further reduced by shear. Before zinc atoms change their coordination under stress, proton mobility increases, i.e., hydrogen atoms start to change the oxygen atom they are bonded to within 10 ps time scales. The hydrostatic stress for this to occur is reduced with increasing shear. Our finding suggests that materials for which number, nature, and mobility of ions are stress sensitive cannot have a well-defined position in the triboelectric series, since local contact stresses generally depend on the stiffness of the counter body. Moreover, our simulations do not support the idea that chemical reactions in a tribo-contact are commonly those that would be obtained through heating alone
Electron beam damage of biological specimens in liquid-phase electron microscopy
Get PDFElectron microscopy of native biological materials is usually hampered by sample preparation procedures such as dehydration and freezing, and by electron beam damage. Liquid phase electron microscopy (LP-EM) allows the observation of biological samples in liquid environments without conventional preparation procedures. However, electron beam damage also occurs in LP-EM, and thresholds for biological samples are not yet fully explored. In this work, the electron dose tolerance of green fluorescent protein (GFP) was analyzed in LP-EM. Protein damage was studied with increasing electron dose, using fluorescence degradation as an indication. Dc < 0.01 e-/Ų and Dc < 0.1 e-/Ų were observed for GFP on silicon nitrite in transmission electron microscopy (TEM) and environmental scanning electron microscopy (ESEM), respectively. In TEM, the dose tolerance was increased by three orders of magnitude when GFP was encapsulated in graphene liquid cells. The dose tolerance of more complex systems was investigated by binding GFP to actin filaments in fixed SKBR3 cells, which showed Dc < 0.1 e-/Ų in TEM and ESEM. In fixed SKBR3 cells, radiation damage was also studied based on the displacement of labeled membrane proteins. At electron doses of D = (7.8 ± 0.4) ∙ 10³ e-/Ų these labels showed a displacement of 0.8%. Procedures for studying biological materials such as proteins and fixed cells in LP-EM are presented in this thesis. Strategies to study and mitigate beam damage are demonstrated.Elektronenmikroskopie nativer biologischer Materialien wird in der Regel durch Probenpräparationsverfahren wie Dehydrierung und Einfrieren sowie durch Strahlenschäden behindert. Flüssigphasen-Elektronenmikroskopie (LP-EM) ermöglicht die Beobachtung biologischer Proben in flüssiger Umgebung ohne herkömmliche Präparationsverfahren. Strahlenschäden treten allerdings auch in LP-EM auf, jedoch sind die Grenzwerte biologischer Proben noch nicht vollständig erforscht. In dieser Arbeit wurde die Dosistoleranz des grün fluoreszierenden Proteins (GFP) in LP-EM analysiert. Proteinschädigung wurde anhand abnehmender Fluoreszenz mit zunehmender Elektronendosis untersucht. Dc < 0.01 e-/Ų und Dc < 0.1 e-/Ų wurden für GFP auf Siliziumnitrit in Transmissionselektronenmikroskopie (TEM) bzw environmental scanning electron microscopy (ESEM) gezeigt. In TEM konnte die Dosistoleranz mit dem Einschluss von GFP in Graphenflüssigzellen um drei Größenordnungen erhöht werden. Zur Untersuchung komplexerer Systemen wurde GFP an Aktinfilamente in SKBR3 Zellen gebunden, die Dc < 0.1 e-/Ų in TEM und ESEM zeigten. In fixierten SKBR3-Zellen wurden Strahlenschäden auch anhand der Verschiebung markierter Membranproteine untersucht. Bei D = (7.8 ± 0.4) ∙ 10³ e-/Ų zeigten diese eine Verschiebung von 0.8%. In dieser Arbeit werden Verfahren zur Untersuchung biologischer Materialien wie Proteinen und fixierten Zellen in LP-EM vorgestellt. Strategien zur Untersuchung und Abschwächung von Strahlenschäden werden aufgezeigt
Two-photon sensitive biomaterials for dynamic control of cellular microenvironments
Get PDFTwo-photon (2P) activable photocleavable protecting groups (PPGs) can be introduced in polymer networks as photodegradation sites or as blocking groups for active sites, which enable the alternation of mechanical properties and biochemical signals and allow to study consequent cell response in a spatiotemporal controlled manner. So far, the design of high efficient 2P activable hydrogels is challenging. This Thesis presents novel designs of photodegradable hydrogels that contain the 4’-methoxy-4-nitrobiphenyl-3-yleth-2-yl)methyl (PMNB) PPG. PMNB-gels formed under physiological conditions and showed tuneable hydrolytic stability and adequate rate for cell encapsulation. Moreover, PMNB-gels can be photodegraded efficiently upon 2P excitation (λ = 740 nm). Preliminary experiments of PMNB-gels as 4D matrices for the investigation of cell response are presented. In a second part, a 2P-activatable PPGs endowed with an extended π conjugation was demonstrated and introduced to yield the RGD cell adhesive peptide. The targeted peptide is obtained but only in low yield due to its low stability. The results of this Thesis provide new tools for instructing cells in 3D cultures using 2P-activated processes and demonstrate the potential of photochemistry for the realization of 4D biomaterials.Zwei-Photonen-(2P)-aktivierbare photolytisch spaltbare Schutzgruppen (PPGs) können in Polymernetzwerke als photokysestellen oder als Schutzgruppen für aktive Stellen eingeführt werden, das Alternieren von mechanischen Eigenschaften und biochemischen Signalen ermöglichen und es erlauben, die daraus resultierende Zellreaktion in einer räumlich-zeitlich kontrollierten Weise zu untersuchen. Bisher ist das Design von hocheffizienten 2P-aktivierbaren Hydrogelen eine Herausforderung. In dieser Arbeit werden neuartige Designs von photodegradierbaren Hydrogelen vorgestellt, die 4'-Methoxy-4-nitrobiphenyl-3-yleth-2-yl)methyl (PMNB) PPG enthalten. PMNB-Gele bildeten sich unter physiologischen Bedingungen und zeigten eine einstellbare hydrolytische Stabilität und eine angemessene Geschwindigkeit für die Immobilisierung von Zellen. Darüber hinaus können PMNB-Gele bei 2P-Anregung (λ = 740 nm) effizient photolytisch abgebaut werden. Es werden erste Experimente mit PMNB-Gelen als 4D-Matrizen für die Untersuchung der Zellreaktion vorgestellt. In einem zweiten Teil wurde ein eine 2P-aktivierbares PPGs mit einer verlängerten π-Konjugation demonstriert und eingeführt, um das zelladhäsive RGD-Peptid zu erhalten. Das angestrebte Peptid wurde gewonnen, allerdings aufgrund seiner geringen Stabilität nur in geringer Ausbeute. Die Ergebnisse dieser Arbeit liefern neue Werkzeuge für die Steuerung von Zellen in 3D-Kulturen mit Hilfe von 2P-aktivierbaren Prozessen und zeigen das Potenzial der Photochemie für die Realisierung von 4D-Biomaterialien
Dual-Use of Seawater Batteries for Energy Storage and Water Desalination
Get PDFSeawater batteries are unique energy storage systems for sustainable renewable energy storage by directly utilizing seawater as a source for converting electrical energy and chemical energy. This technology is a sustainable and cost-effective alternative to lithium-ion batteries, benefitting from seawater-abundant sodium as the charge-transfer ions. Research has significantly improved and revised the performance of this type of battery over the last few years. However, fundamental limitations of the technology remain to be overcome in future studies to make this method even more viable. Disadvantages include degradation of the anode materials or limited membrane stability in aqueous saltwater resulting in low electrochemical performance and low Coulombic efficiency. The use of seawater batteries exceeds the application for energy storage. The electrochemical immobilization of ions intrinsic to the operation of seawater batteries is also an effective mechanism for direct seawater desalination. The high charge/discharge efficiency and energy recovery make seawater batteries an attractive water remediation technology. Here, the seawater battery components and the parameters used to evaluate their energy storage and water desalination performances are reviewed. Approaches to overcoming stability issues and low voltage efficiency are also introduced. Finally, an overview of potential applications, particularly in desalination technology, is provided
Ameboid cell migration through regular arrays of micropillars under confinement
No full textMigrating cells often encounter a wide variety of topographic features—including the presence of obstacles—when navigating through crowded biological environments. Unraveling the impact of topography and crowding on the dynamics of cells is key to better understand many essential physiological processes such as the immune response. We study the impact of geometrical cues on ameboid migration of HL-60 cells differentiated into neutrophils. A microfluidic device is designed to track the cells in confining geometries between two parallel plates with distance , in which identical micropillars are arranged in regular pillar forests with pillar spacing . We observe that the cells are temporarily captured near pillars, with a mean contact time that is independent of and . By decreasing the vertical confinement , we find that the cell velocity is not affected, while the persistence reduces; thus, cells are able to preserve their velocity when highly squeezed but lose the ability to control their direction of motion. At a given , we show that by decreasing the pillar spacing in the weak lateral confinement regime, the mean escape time of cells from effective local traps between neighboring pillars grows. This effect, together with the increase of cell-pillar contact frequency, leads to the reduction of diffusion constant . By disentangling the contributions of these two effects on in numerical simulations, we verify that the impact of cell-pillar contacts on cell diffusivity is more pronounced at smaller pillar spacing
High-Entropy Sulfides as Electrode Materials for Li-Ion Batteries
Get PDFAbstract High-entropy sulfides (HESs) containing 5 equiatomic transition metals (M), with different M:S ratios, are prepared by a facile one-step mechanochemical approach. Two new types of single-phase HESs with pyrite (Pa-3) and orthorhombic (Pnma) structures are obtained and demonstrate a homogeneously mixed solid solution. The straightforward synthesis method can easily tune the desired metal to sulfur ratio for HESs with different stoichiometries, by utilizing the respective metal sulfides, even pure metals, and sulfur as precursor chemicals. The structural details and solid solution nature of HESs are studied by X-ray diffraction, transmission electron microscopy, energy-dispersive X-ray spectroscopy, electron energy loss spectroscopy, X-ray photoelectron spectroscopy, inductively coupled plasma optical emission spectroscopy, and Mössbauer spectroscopy. Since transition metal sulfides are a very versatile material class, here the application of HESs is presented as electrode materials for reversible electrochemical energy storage, in which the HESs show high specific capacities and excellent rate capabilities in secondary Li-ion batteries