Publikationen

Antimicrobial resistance is a global crisis driven by a scarce pipeline of new antibiotics. A major contributor is the intrinsic resistance conferred by the bacterial envelope, highlighting the need for innovative molecules for improved therapies. In this study, TAT–ArgBD, a conjugate of the cell-penetrating TAT peptide and arginine biodynamer (ArgBD), serves in vitro as a multivalent macromolecular antibiotic and synergist. TAT–ArgBD rapidly kills 99.9% of Pseudomonas aeruginosa at 32 µg/mL within 1 h, outperforming colistin, and shows minimum inhibitory concentrations (MICs) of 2–8 µg/mL against Acinetobacter baumannii and Staphylococcus aureus. Notably, it potentiates antibiotics such as novobiocin, chloramphenicol, and imipenem, leading to lowered MICs up to 256-fold. Notably, novobiocin, typically active only against Gram-positive bacteria, showed activity against Gram-negative bacteria when combined with TAT–ArgBD. Mechanistic studies suggest TAT–ArgBD antimicrobial and synergistic actions result from preferential binding to POPG and cardiolipin. This interaction induces bacterial membrane pore formation by adopting an α-helical conformation in the presence of bacterial lipids. With a favorable in vitro safety profile, a membranolytic index > 64 and low mammalian cell toxicity at effective bactericidal concentrations, TAT–ArgBD’s potential to enhance antibiotic efficacy, as well as function as a stand-alone treatment, supports further preclinical evaluation as an antimicrobial adjuvant.

Living therapeutic materials (LTMs) are an emerging class of biomaterials that integrate living cells within engineered polymer matrices to provide dynamic and responsive functionalities. In this study, we engineered the robust, nonpathogenic, and GRAS-certified microorganism Corynebacterium glutamicum into a multifunctional biofactory for LTM applications. Using synthetic biology, we designed and constructed C. glutamicum strains capable of sensing, reporting, and producing the extremolyte ectoine. Ectoine is a clinically used compatible solute with cytoprotective and anti-inflammatory properties that is widely applied in dermatological formulations, nasal sprays, and ophthalmic preparations for the treatment of inflammatory and stress-related conditions. The engineered strains were further encapsulated in polymer-based living materials, including membrane-in-gel patches and core–shell hydrogel systems, to create skin-compatible and ocular-applicable therapeutic platforms. We developed genetic biosensors that detect diaminobutyric acid (DABA), a key intermediate in the ectoine biosynthesis pathway, to enable the time-resolved monitoring of cellular function. These biosensors, which are integrated with fluorescence and enzymatic reporter systems, allowed the noninvasive visualization of metabolic activity. Encapsulation strategies were optimized to ensure high metabolic activity, structural stability, and biocontainment, along with the controlled release of ectoine for potential applications in drug delivery and protective therapies. This work highlights the potential of C. glutamicum as a versatile platform for next-generation LTMs, offering precise monitoring and targeted therapeutic capabilities toward multifunctional living materials for precision medicine and environmental biosensing applications.

In this work, hierarchically porous materials have been prepared by the self-assembly and pore formation of different amphiphilic block copolymers (BCPs) in the vicinity of cellulose paper sheets. For this, polystyrene-block-polysolketal methacrylate (PS-b-SMA) as a linear BCP and polymethyl methacrylate-block-polysolketal methacrylate (PMMA-b-SMA)n as a star-shaped BCP were prepared using living anionic polymerization. Under mild acidic conditions, the amphiphilic properties were revealed by converting the PSMA block segment to poly(dihydroxypropyl methacrylate) (PDHPMA). The BCPs were incorporated onto cellulose linters fiber-based sheets by a self-assembly and nonsolvent-induced phase separation (SNIPS) process. The resulting porous materials have been further modified with 3-aminopropyltriethoxysilane (APTES) and 3,3,3-trifluoropropyl dimethyl chlorosilane (TFPCS) using a vapor-phase modification approach. This strategy enabled further tuning of the surface properties of the resulting porous structures to adjust surface polarity. The characteristics of the modified porous materials were confirmed at the microscopic scale by solid-state nuclear magnetic resonance (NMR) combined with selectively enhanced dynamic nuclear polarization (DNP) and Fourier transform infrared (FTIR) spectroscopy. The influence of APTES and TFPCS was further analyzed at the macroscopic level using water contact angle (WCA) measurements and water permeance testing, where changes were observed for both modifiers. Using this convenient strategy, the fabrication of functional porous cellulose composite materials is demonstrated, paving the way for a new family of cellulose-based porous materials.

Sponges are simple metazoans that build hierarchical mineral-organic architectures under ambient conditions, offering bioinspiration for lightweight, damage-tolerant structural materials. Yet the multiscale mechanics of freshwater sponges remain unexplored compared with well-studied marine species. Here we report the first quantitative investigation of an Amazonian freshwater sponge (Cauxi), linking its biogenic silica spicules and a double-shell, spicule-reinforced gemmule capsule to survival under alternating aquatic and subaerial conditions. Multiscale structural characterization combined with micro-/nanomechanical testing reveals that the silica spicules in Cauxi exhibit lower stiffness and toughness than fused glass, consistent with their amorphous, nanoporous structure. Micropillar tests show no statistically significant orientation dependence within experimental uncertainty, reflecting the spicules’ amorphous character. The gemmule architecture—two shells separated by a lightweight foam and reinforced by short spicules with star-like outer tips and disk-like inner bases—resists localized loading and suggests shell-buckling and rib-stiffening as operative protection principles. Building on these observations, we provide simple scaling arguments and testable predictions for buoyancy, dispersal by damage tolerance, positioning Cauxi as a model for lightweight, damage-tolerant capsules and short-fiber-reinforced composites formed under ambient conditions. These results articulate environment-specific structure–property trade-offs and offer generalizable cues for architected structural materials.

The gut microbiota, immune system, and enteric nervous system interact to regulate adult gut physiology. However, the mechanisms establishing gut physiology during development remain unknown. We report that in developing zebrafish, enteroendocrine cells produced interleukin-22 (IL-22) in response to microbial signals before lymphocytes populated the gut. In larvae, IL-22 shaped the gut microbiota, increasing Lactobacillaceae abundance and ghrelin expression to promote gut motility. Impaired motility and ghrelin expression were restored in il22−/− zebrafish by transfer of microbiota from wild-type zebrafish or by introducing only Lactobacillus plantarum. IL-22–deficient mice also had impaired gut motility and reduced ghrelin expression in early life, indicating a conserved function. Thus, before immune system maturation, enteroendocrine cells regulate early-life gut function by controlling the microbiota through IL-22.

The development of efficient carbon-based materials is crucial for overcoming the performance limitations of traditional electrodes in capacitive deionization (CDI). However, the practical performance of heteroatom-doped carbon electrodes for desalination in complex multi-ion water matrices remains largely unexplored. In this work, we studied the ion selectivity toward Li+ and the removal efficiency of nitrogen‑sulfur co-doped and boron-doped carbon electrodes in brackish water, using multi-salt cation solutions containing monovalent (Li+, Na+, K+) and divalent (Ca2+, Mg2+) ions. These modifications enhanced charge distribution, wettability, and ion diffusion within the electrodes. As a result, the N,S-AC electrode exhibited pronounced lithium selectivity in brackish water, while the B-AC electrode delivered higher adsorption capacity. The B-AC electrode achieved both high capacity and enhanced lithium selectivity even under strong competition from Na+, Mg2+, and Ca2+. These findings demonstrate the distinct and complementary roles of N,S-co-doping and B-doping, offering valuable insights into how heteroatom engineering can advance CDI performance.

Transition metal oxalates have been proven to be a promising electrode material for lithium-ion batteries. Here, we have designed a series of multi-phase transition metal oxalates with different structures and compositions by simply adjusting the proportions of five transition metal elements. Among them, the multi-phase mixture (MC2O4·2H2O – CuC2O4 – MC2O4·2H2O, M = Mn, Fe, Co, Ni, Cu) provides a more stable framework for the material during lithiation and delithiation, effectively alleviating the structural collapse during the cycling process. In addition, the electron transport and fast charge compensation processes of multiple electrochemically active metal pairs also contribute to the improvement of performance. Therefore, the multi-phase transition metal oxalate TMOx-2 electrode with an additional CuC2O4 phase exhibits high reversible capacity and long-term cycling stability. After 400 cycles at 100 and 500 mA/g, the specific discharge capacities are 827 mAh/g and 498 mAh/g, respectively. Constructing multi-metal, multi-phase systems by combining different transition metals enables control over potential, reaction pathways, and stability of high-performance electrodes.

Lipid vesicles are important as minimal model systems for cellular compartmentalization. They drive major advances in deciphering biological mechanisms by molecular reconstitution; provide rational solutions for primitive compartmentalization in origin-of-life studies; form the basis of synthetic cells and drug delivery vehicles. The emulsion method is a well-established route for producing bilayer lipid vesicles. However, the application of this method in microfluidics requires complex and specialized machinery. The bulk method suffers from the need to physically manipulate the vesicles through oil layers for characterization that can damage the vesicles. Given this, we present a facile and robust method for on-chip production and manipulation of lipid vesicles by the emulsion method. We prepared a simple device that allows preparation, imaging, and collection of activated lipid vesicles. This technique combines minimal processing steps with maximum flexibility in lipid vesicle production and manipulation with direct imaging, thus fast-tracking production lines across disciplines.

Catechol-modified polymers, such as DOPA-functionalized systems, have recently gained significant interest for a variety of biomedical applications, particularly in their role as antibacterial adjuvants due to their oxidative activity and ability to generate reactive oxygen species (ROS). Current catechol-functionalized polymers, however, often suffer from a restricted number of catechol groups, limited biocompatibility and solubility, and low stability due to the rapid oxidation under physiological conditions. In this study, we developed a water-soluble, biocompatible DOPA-modified biodynamer (DOPA-BD), leveraging the principles of constitutional dynamic chemistry (CDC). DOPA-BD was synthesized via polycondensation of DOPA-hydrazide and the hexaethylene glycol-conjugated carbazole dialdehyde (CA-HG), forming dynamic imine and acylhydrazone linkages between the monomers. As a result of its dynamic covalent backbone, DOPA-BD exhibits biodegradability and undergoes pH-responsive degradation under mildly acidic conditions typically found at infection sites, leading to a more than 3-fold increase in DOPA-hydrazide release compared to physiological pH. Interestingly, driven by CDC, DOPA-BD folds into a nanorod structure with a hydrodynamic diameter of ∼7.8 nm, surrounded by HG chains that offer water solubility and biocompatibility. Moreover, the incorporation of the DOPA-derivative in each repeating unit yields a polymer with exceptionally high catechol content, which remains stable and resistant to oxidation for 72 h in physiological buffer conditions. Regarding its antibacterial applicability, DOPA-BD demonstrated synergistic antibacterial activity with Azithromycin (AZM) against AZM-resistant E. coli, enhancing the antibiotic’s efficacy by 4-fold. Our study indicates that DOPA-BD induces ROS production in the respective bacterial strain, suggesting ROS generation as one of the possible mechanisms contributing to the observed synergy. Overall, DOPA-BD represents a promising alternative strategy to potentiate antibacterial activity against resistant strains, holding strong potential for future antibacterial applications.

The functional integration of biological switches with synthetic building blocks enables the design of modular, stimulus-responsive biohybrid materials. By connecting the individual modules via diffusible signals, information-processing circuits can be designed. Such systems are, however, mostly limited to respond to either small molecules, proteins, or optical input thus limiting the sensing and application scope of the material circuits. Here, a highly modular biohybrid material is design based on CRISPR/Cas13a to translate arbitrary single-stranded RNAs into a biomolecular material response. This system exemplified by the development of a cascade of communicating materials that can detect the tumor biomarker microRNA miR19b in patient samples or sequences specific for SARS-CoV. Specificity of the system is further demonstrated by discriminating between input miRNA sequences with single-nucleotide differences. To quantitatively understand information processing in the materials cascade, a mathematical model is developed. The model is used to guide systems design for enhancing signal amplification functionality of the overall materials system. The newly designed modular materials can be used to interface desired RNA input with stimulus-responsive and information-processing materials for building point-of-care suitable sensors as well as multi-input diagnostic systems with integrated data processing and interpretation.