Publikationen

Many biological active agents respond to gradients of environmental cues by redirecting their motion. In addition to the well-studied prominent examples such as phototaxis and chemotaxis, there has been considerable recent interest in topotaxis, i.e., the ability to sense and follow topographic environmental cues. A trivial topotaxis is achievable through a spatial gradient of obstacle density, though over limited length scales. Here, we introduce a type of topotaxis based on sliding of particles along obstacles—as observed, e.g., in bacterial dynamics near surfaces. We numerically demonstrate how imposing a gradient in the angle of sliding along pillars breaks the spatial symmetry and biases the direction of motion, resulting in an efficient topotaxis in a uniform pillar park. By repeating blocks of pillars with a strong gradient of sliding angle, we propose an efficient method for guiding particles over arbitrary long distances. We provide an explanation for this spectacular phenomenon based on effective reflection at the borders of neighboring blocks. Our results are of technological and medical importance for design of efficient taxis devices for living agents.

Hybrid hydrogels are hydrogels that exhibit heterogeneity in the network architecture by means of chemical composition and/or microstructure. The different types of interactions, together with structural heterogeneity, which can be created on different length scales, determine the mechanical properties of the final material to a large extent. In this work, the microstructure–mechanical property relationships for a hybrid hydrogel that contains both electrostatic and covalent interactions are investigated. The hybrid hydrogel is composed of a microphase-separated polyelectrolyte complex network (PEC) made of poly(4-styrenesulfonate) and poly(diallyldimethylammonium chloride) within a soft and elastic polyacrylamide hydrogel network. The system exhibits a granular structure, which is attributed to the liquid–liquid phase separation into complex coacervate droplets induced by the polymerization and the subsequent crowding effect of the polyacrylamide chains. The coacervate droplets are further hardened into PEC granules upon desalting the hydrogel. The structure formation is confirmed by a combination of electron microscopic imaging and molecular dynamics simulations. The interpenetration of both networks is shown to enhance the toughness of the resulting hydrogels due to the dissipative behavior of the PEC through the rupture of electrostatic interactions. Upon cyclic loading–unloading, the hydrogels show recovery of up to 80% of their original dissipative behavior in less than 300 s of rest with limited plasticity. The granular architecture and the tough and self-recoverable properties of the designed hybrid networks make them good candidates for applications, such as shape-memory materials, actuators, biological tissue mimics, and elastic substrates for soft sensors.

We study the effect of additives on the colloidal stability of alkanethiol-coated gold nanoparticles. Cyclic amines and sulfides of different sizes were added to dispersions in decane at additive concentrations below 128 mM. Small-angle X-ray scattering (SAXS) indicated that tetrahydrothiophene reduced the agglomeration temperature, Tagglo, by up to 29 °C, a considerable increase in colloidal stability. Amines had a much weaker stabilizing effect of up to 2.5 °C. We found an unexpected maximum of stabilization for low additive concentrations, where Tagglo increased at concentrations above 64 mM. Molecular dynamics simulations were used to correlate these observations with the ligand shell structure. They excluded the physisorption of additives as a stabilization mechanism and suggested that sulfides replace hexadecanethiol on the AuNP surfaces by chemisorption. This hinders ligand ordering, thereby reducing Tagglo, which explains the stabilizing effect. Clustering of chemisorbed additive molecules at high concentration restabilized the ligand ordered state, explaining the detrimental effect of higher additive concentrations. The predictions of the simulations were confirmed by using thermogravimetric analyses and SAXS measurements of washed samples that indicated that the structure of the ligand shell itself, not the presence of physisorbed additives, changes Tagglo. Finally, we calculated potentials of mean force, which show that larger sulfide-based additives have a weaker affinity for the gold surface than smaller ones due to stronger steric hindrance. This explains why smaller cyclic sulfides were the most efficient stabilizers.

Pulmonary fibrosis, a disabling lung disease, results from the fibrotic transformation of lung tissue. This fibrotic transformation leads to a deterioration of lung capacity, resulting in significant respiratory distress and a reduction in overall quality of life. Currently, the frontline treatment of pulmonary fibrosis remains limited, focusing primarily on symptom relief and slowing disease progression. Bacterial infections with Pseudomonas aeruginosa are contributing to a severe progression of idiopathic pulmonary fibrosis. Phytic acid, a natural chelator of zinc, which is essential for the activation of metalloproteinase enzymes involved in pulmonary fibrosis, shows potential inhibition of LasB, a virulence factor in P. aeruginosa, and mammalian metalloproteases (MMPs). In addition, phytic acid has anti-inflammatory properties believed to result from its ability to capture free radicals, inhibit certain inflammatory enzymes and proteins, and reduce the production of inflammatory cytokines, key signaling molecules that promote inflammation. To achieve higher local concentrations in the deep lung, phytic acid was spray dried into an inhalable powder. Challenges due to its hygroscopic and low melting (25 °C) nature were mitigated by converting it to sodium phytate to improve crystallinity and powder characteristics. The addition of leucine improved aerodynamic properties and reduced agglomeration, while mannitol served as carrier matrix. Size variation was achieved by modifying process parameters and were evaluated by tools such as the Next Generation Impactor (NGI), light diffraction methods, and scanning electron microscopy (SEM). An inhibition assay for human MMP-1 (collagenase-1) and MMP-2 (gelatinase A) allowed estimation of the biological effect on tissue remodeling enzymes. The activity was also assessed with respect to inhibition of bacterial LasB. The formulated phytic acid demonstrated an IC50 of 109.7 µg/mL for LasB with viabilities > 80 % up to 188 µg/mL on A549 cells. Therefore, inhalation therapy with phytic acid-based powder shows promise as a treatment for early-stage Pseudomonas-induced pulmonary fibrosis.

The expansion of T cells ex vivo is crucial for effective immunotherapy but currently limited by a lack of expansion approaches that closely mimic in vivo T cell activation. Taking inspiration from bottom-up synthetic biology, a new synthetic cell technology is introduced based on dispersed liquid-liquid phase-separated droplet-supported lipid bilayers (dsLBs) with tunable biochemical and biophysical characteristics, as artificial antigen presenting cells (aAPCs) for ex vivo T cell expansion. These findings obtained with the dsLB technology reveal three key insights: first, introducing laterally mobile stimulatory ligands on soft aAPCs promotes expansion of IL-4/IL-10 secreting regulatory CD8+ T cells, with a PD-1 negative phenotype, less prone to immune suppression. Second, it is demonstrated that lateral ligand mobility can mask differential T cell activation observed on substrates of varying stiffness. Third, dsLBs are applied to reveal a mechanosensitive component in bispecific Her2/CD3 T cell engager-mediated T cell activation. Based on these three insights, lateral ligand mobility, alongside receptor- and mechanosignaling, is proposed to be considered as a third crucial dimension for the design of ex vivo T cell expansion technologies.

Zhu et al. introduce MELG (materials engineered by living grafting), combining engineered microbes with non-living scaffolds for functional protein regeneration within. These MELGs can be used for long-term controlled release, enzyme-mediated biocatalysis, and DNA purification. This approach offers enhanced functionality and durability in bioactive materials compared to traditional non-living counterparts.

Background: Tumor cells release extracellular vesicles (EVs) that contribute to the polarization of macrophages towards tumor-associated macrophages (TAMs). High expression levels of the RNA binding protein IGF2BP2/IMP2 are correlated with increased tumor cell proliferation, invasion, and poor prognosis in the clinic. However, there is a lack of understanding of whether IMP2 affects the cargo of cancer cell-derived EVs, thereby modulating macrophage polarization.
Methods: EVs were isolated from IMP2-expressing HCT116 parental cells (WT) and CRISPR/Cas9 IMP2 knockout (KO) cells. EVs were characterized according to MISEV guidelines, microRNA cargo was assessed by microRNA-Seq, and the protein cargo was analyzed by proteomics. Primary human monocyte-derived macrophages (HMDMs) were polarized by EVs, and the expression of genes and surface markers was assessed using qPCR and flow cytometry, respectively. Morphological changes of macrophages, as well as the migratory potential of cancer cells, were assessed by the Incucyte® system and macrophage matrix degradation potential by zymography. Changes in the metabolic activity of macrophages were quantified using a Seahorse® analyzer. For in vivo studies, EVs were injected into the yolk sac of zebrafish larvae, and macrophages were isolated by fluorescence-activated cell sorting.
Results: EVs from WT and KO cells had a similar size and concentration and were positive for 25 vesicle markers. The expression of tumor-promoting genes was higher in macrophages polarized with WT EVs than KO EVs, while the expression of TNF and IL6 was reduced. A similar pattern was observed in macrophages from zebrafish larvae treated in vivo. WT EV-polarized macrophages showed a higher abundance of TAM-like surface markers, higher matrix degrading activity, as well as a higher promotion of cancer cell migration. MicroRNA-Seq revealed a significant difference in the microRNA composition of WT and KO EVs, particularly a high abundance of miR-181a-5p in WT EVs, which was absent in KO EVs. Inhibitors of macropinocytosis and phagocytosis antagonized the delivery of miR-181a-5p into macrophages and the downregulation of the miR-181a-5p target DUSP6. Proteomics data showed differences in protein cargo in KO vs. WT EVs, with the differentially abundant proteins mainly involved in metabolic pathways. WT EV-treated macrophages exhibited a higher basal oxygen consumption rate and a lower extracellular acidification rate than KO EV-treated cells.
Conclusion: Our results show that IMP2 determines the cargo of EVs released by cancer cells, thereby modulating the EVs' actions on macrophages. Expression of IMP2 is linked to the secretion of EVs that polarize macrophages towards a tumor-promoting phenotype.

Microporous carbonaceous electrode materials store charge by ion electrosorption onto the electrode surface. Despite significant efforts to understand this phenomenon, a definitive picture of the adsorption mechanisms within these complex nanoscale structures is lacking. Here, we use nuclear magnetic resonance (NMR) spectroscopy to directly observe and quantify aqueous adsorbate partitioning behavior driven by spontaneous physisorption within the micropores. Our results show that the solvation properties of the electrolyte ions influence the ionophilicity/ionophobicity of the adsorbate-carbon system, with ionophilic and ionophobic systems exhibiting distinct behavior concerning the electrolyte loading volume. Micropore diameter is also shown to influence spontaneous electrolyte partitioning behavior and disturb ion solvation. In situ NMR spectroscopy using a working supercapacitor comprising microporous carbon electrodes with aqueous sodium sulfate and aqueous sodium bis(trifluoromethane)sulfonimide electrolytes indicates that spontaneous electrolyte partitioning behavior influences the charge-balancing mechanism. Our results suggest that spontaneously ionophilic systems favor charge-balancing by counter-ion adsorption under an applied voltage, and spontaneously ionophobic systems favor a co-ion ejection mechanism under an applied potential. These results provide new molecular-level insight into the role of electrolyte properties on spontaneous physisorption behavior and charged electrosorption behavior within microporous carbon electrodes.

Glycerol is a widely used signaling bioanalyte in biotechnology. Glycerol can serve as a substrate or product of many metabolic processes in cells. Therefore, quantification of glycerol in fermentation samples with inexpensive, reliable, and rapid sensing systems is of great importance. In this work, an amperometric assay based on one-step designed electroplated functional Pd layers with controlled design was proposed for a rapid and selective measurement of glycerol in yeast fermentation medium. A novel assay utilizing electroplated Pd-sensing layers allows the quantification of glycerol in yeast fermentation medium in the presence of interfering species with RSD below 3% and recoveries ranged from 99 to 103%. The assay requires minimal sample preparation, viz. adjusting of sample pH to 12. The time taken to complete the electrochemical analysis was 3 min. Remarkably, during investigations, it was revealed that sensitivity and selectivity of glycerol determination on Pd sensors were significantly affected by its adsorption and did not depend on the surface structure of sensing layers. This study is expected to contribute to both fundamental and practical research fields related to a preliminary choice of functional sensing layers for specific biotechnology and life science applications in the future.

Mechanical metamaterials are known for their prominent mechanical characteristics such as programmable deformation that are due to periodic microstructures. Recent research trends have shifted to utilizing mechanical metamaterials as structural substrates to integrate with functional materials for advanced functionalities beyond mechanical, such as active sensing. This study reports on the ultra-stretchable kirigami piezo-metamaterials (KPM) for sensing coupled large deformations caused by in- and out-of-plane displacements using the lead zirconate titanate (PZT) and barium titanate (BaTiO3) composite films. The KPM are fabricated by uniformly compounding and polarizing piezoelectric particles (i.e., PZT and BaTiO3) in silicon rubber and structured by cutting the piezoelectric rubbery films into ligaments. Characterizes the electrical properties of the KPM and investigates the bistable mechanical response under the coupled large deformations with the stretching ratio up to 200% strains. Finally, the PZT KPM sensors are integrated into wireless sensing systems for the detection of vehicle tire bulge, and the non-toxic BaTiO3 KPM are applied for human posture monitoring. The reported kirigami piezo-metamaterials open an exciting venue for the control and manipulation of mechanically functional metamaterials for active sensing under complex deformation scenarios in many applications.