Publikationen

T cell activation requires cell polarization and changes in gene expression. Target cell stiffness contributes to the activation of immune cells, and tumor cell softening is linked to cancer progression. We investigated how substrate stiffness influences T cell activation using functionalized, T cell–activating substrates of varying stiffness and softened target cells. Reorientation of the microtubule-organizing center (MTOC) toward the immunological synapse and nuclear translocation of the transcription factor NFAT1 were impaired on softer hydrogels or upon contact with softer target cells. The increase in intracellular Ca2+ induced by target engagement also depended on stiffness and was reduced on soft substrates. Stiffness-dependent Ca2+ signaling was crucial for both rapid (MTOC reorientation) and long-term (NFAT translocation) responses. Whereas MTOC reorientation depended on the mechanosensitive Ca2+-permeable channel PIEZO1, NFAT1 translocation depended on the Ca2+ channel ORAI1. Our results demonstrate that target stiffness directly influences MTOC reorientation and NFAT1 translocation in T cells, and these two processes are governed by different plasma membrane Ca2+ channels, indicating that these stiffness-regulated rapid and long-term responses can be decoupled. Our findings imply that tumor cell stiffness regulates T cell functionality and suggest that pathways regulated by PIEZO1 and ORAI1 might differentially control rapid and long-term responses to stiffness in other cell types.

Herein, we report the charge storage and plastic properties of the redox-active, bimetallic metal phosphonate framework of [Cu(2,2′-bpy)VO(O3PC6H5)2]. The flexible crystals of [Cu(2,2′-bpy)VO(O3PC6H5)2] combine high energy storage with mechanical flexibility on the same platform, which is an unusual and significant property that is not observed in traditional rigid layered electrode materials. In contrast to RuO2, graphene, or MXenes, which prefer concentrated acidic or basic electrolytes to operate effectively as electrodes, [Cu(2,2′-bpy)VO(O3PC6H5)2] operates between pH values of 4 and 10 while reaching a specific capacitance of about 140 F/g in H3PO4 at pH 4 and in NaOH at pH 10 at 1 mV/s. It also demonstrates high chemical and electrochemical stability between pH 2 and 12 and in lithium hexafluorophosphate for extended periods. The use of [Cu(2,2′-bpy)VO(O3PC6H5)2] as electrodes eliminates the need for harsh chemical environments, generating more sustainable and environmentally friendly energy storage solutions, and [Cu(2,2′-bpy)VO(O3PC6H5)2] can be synthesized in water at mild temperatures. The combination of chemical stability, mechanical flexibility of [Cu(2,2′-bpy)VO(O3PC6H5)2], and compatibility with mild electrolytes makes [Cu(2,2′-bpy)VO(O3PC6H5)2] a more sustainable alternative to conventional metal oxides, MXenes, and carbon-based electrodes in next-generation supercapacitors and battery technologies.

Hydrogels mimicking the mechanical and biochemical features of the cellular microenvironment allow cell encapsulation and facilitate in vitro 3D culture. In addition to biocompatibility and reactivity in physiological conditions, a key criterion for crosslinking chemistry is appropriate gelation kinetics to allow mixing and homogeneous distribution of cells with the hydrogel precursors. We have previously presented aryl methylsulfone/thiol (MS/SH) reaction as a thiol-reactive cross-linking system for cell encapsulation in star polyethylene glycol (PEG4) hydrogels with a gelation kinetics in minutes time scale. Remaining experimental challenges for this system are a finer modulation of gelation kinetics and streamlining the synthesis of the prepolymer. Here we present the possibility to tune the gelation kinetics by introducing an electron-withdrawing substituent at p-position of the aryl MS ring. This variant also presents synthetic advantages. We study the influence of the p-substituent on the physicochemical properties of MS/SH crosslinked hydrogels, and their performance for cell encapsulation. We compare these properties with the PEG-MS variant containing an electron-donating linker. The new star poly(ethylene glycol)-4-(5-(methylsulfonyl)-1H-tetrazol-1-yl)benzamide (PEG4-CONH-TzMS) shows superior properties as cell encapsulating hydrogel in terms of ease of mixing polymer precursors, faster gelation, homogenous cell distribution and high enzymatic stability.

Excessive protease activity and impaired tissue regeneration are hallmarks of many disease states. Elevated matrix metalloproteinase-9 (MMP-9) plays a key role in adverse tissue remodeling by excessively degrading extracellular matrix (ECM) components and growth factors. Tissue inhibitor of metalloproteinase-3 (TIMP-3) regulates ECM turnover, and its bioavailability is influenced by glycosaminoglycans (GAGs). This study aimed to develop a methacrylated gelatin (GelMA)-based hydrogel functionalized with acrylated sulfated hyaluronan (sHAc) as a TIMP-3 delivery system to decrease ECM degradation under pathophysiological conditions. sHAc incorporation enhanced hydrogel stiffness, reduced degradation rates and yielded sustained TIMP-3 release for up to 28 days. Molecular modeling and surface plasmon resonance demonstrated preferential binding of TIMP-3 to sHAc over hyaluronan methacrylates, together providing a molecular rationale for the reduced and sustained release of TIMP-3 from sHAc-containing hydrogels. Angiogenesis-related functional assays, supported by molecular modeling studies, indicate that sHAc modulates the anti-angiogenic activity of TIMP-3 by altering vascular endothelial growth factor receptor-associated signaling, while preserving metalloproteinase inhibition. Released TIMP-3 from GelMA/sHAc hydrogels retained bioactivity, effectively inhibiting MMP-9 activity and mitigating ECM degradation in-vitro and in human ex-vivo models. In a murine subcutaneous implantation model, sHAc-functionalized TIMP-3-loaded hydrogels were associated with reduced inflammatory cell presence and altered vascular- and matrix-related tissue signatures compared with GelMA controls. These findings underscore the potential of sHAc-functionalized GelMA hydrogels as biomaterials for therapeutics delivery, offering controlled TIMP-3 release and sustained bioactivity to promote ECM stability and on-demand MMP inhibition. This system represents a promising strategy for addressing the challenges of excessive MMP activity.

The demand for lithium production has seen a significant rise, with the growing electric vehicle and stationary battery markets requiring further development of sustainable and scalable extraction methods. Direct lithium extraction technologies have been developed to address potential shortages, with adsorption emerging as a key method due to its efficiency and low environmental impact. Given that Al(OH)3 is already utilized as an adsorbent in various industrial applications, the practical importance of Al-based alternative systems for lithium ion extraction is increasing, yet lithium ion recovery requires harsh chemicals. In this study, we report a novel lithium extraction method combining chemical adsorption and electrochemical release using a synthesized aluminum layered double hydroxide (Al-LDH) material, developed under mild reaction conditions. The performance of the Al-LDH electrode was evaluated against a commercial Al(OH)3 adsorbent. Comprehensive characterization using techniques such as X-ray diffraction, Fourier-transform infrared spectroscopy, and scanning electron microscopy revealed detailed insights into the crystalline structure, particle size distribution, and surface morphology of the materials. The Al-LDH electrode exhibited a lithium ion adsorption capacity, achieving an average chemical uptake of lithium ions of 57.6 mg/g. In contrast, lithium-ion uptake capacity for Al(OH)3 was 1.0 mg/g over 15 cycles. Notably, this method operates under pH-neutral conditions, eliminating the need for harsh acidic or basic eluents. As a result, it prevents structural degradation and minimizes secondary pollution for potential future applications of lithium-ion recovery. The material’s layered structure selectively allowed lithium ion intake while blocking sodium ions, demonstrating its high selectivity and utility in lithium ion recovery processes. The integration of pH-neutral regeneration and high selectivity shows that Al-LDH electrodes as viable candidates for next-generation, green lithium extraction technologies.

Hematopoietic stem cells (HSCs) receive a combination of biochemical and biomechanical signals within the bone marrow that guide their differentiation process. These include soluble factor signaling with cytokines, cellular confinement in the stem cell niche, and contact-dependent receptor–ligand interactions with stromal cells. Recreating this complex microenvironment in vitro is a principal engineering challenge for regenerative therapies and tissue engineering. While cytokines can be easily supplemented in vitro, and several systems for confined HSC culture have been developed, integrating receptor-based intercellular interactions found in stem cell niches has only been achieved with quantitatively undefined heterotypic co-cultures. We report here the development of microwell-based systems that integrate synthetic cells to mimic receptor–ligand interactions within hematopoietic niches. The synthetic cells are based on droplet-supported lipid bilayers (dsLBs) with cytomimetic stiffness and present Notch receptor ligands on a laterally mobile lipid membrane. We show the system's applicability to individually tune the three signaling axes: soluble factors, confinement, and intercellular interactions for HSC differentiation. Introducing synthetic cells as an alternative to coculture and feeder cells opens the possibility to engineer precisely defined HSC niches with adjustable biochemical and biomechanical properties.

The increasing demand for sustainable energy storage drives the development of advanced lithium-ion battery (LIB) materials that combine high performance, cost efficiency, and environmental sustainability. Carbon spherogels, characterized by high surface area, interconnected porosity, and high conductivity, are promising electrode candidates; however, they suffer from low specific capacities when used alone. This study presents iron-loaded carbon spherogels as next-generation LIB electrodes, leveraging iron’s high theoretical capacity, abundance, and eco-friendliness. A scalable and tailorable synthesis method enabled the integration of tunable iron contents (15–40 mass %) into the carbon framework, forming robust porous networks with uniformly distributed iron nanoparticles. Electrochemical characterization revealed high specific capacities (up to 1190 mAh g–1) and high cycling stability (>99% Coulombic efficiency over 300 cycles). Post-mortem analysis highlighted the synergistic interaction between iron redox activity and carbon matrix stability. The medium (27 mass %) iron-loaded carbon spherogel sample achieved the best balance between capacity and durability. These findings position iron-loaded carbon spherogels as sustainable, high-performance LIB electrodes, offering a cobalt-free and nickel-free alternative that addresses key challenges of conversion-type materials, such as volume expansion and capacity fading.

Electrochemical desalination is a promising technology for the selective recovery of Lithium-ions or other rare ions from spent electronics, contributing to a circular economy. Due to its high-energy efficiency and selective Lithium-ion recovery, this method offers a low environmental impact, making it a promising tool for recovering Lithium-ions from spent batteries. Few studies have examined electrochemical desalination as a tool to recover Lithium-ions from real spent battery solutions. In this work, solutions obtained from real shredding of Lithium-iron-phosphate (LFP) batteries inside a cooling water reservoir were used as a Lithium-rich source to obtain a high-purity Lithium-ion recovery solution. A 96%-pure Lithium-ion recovery solution was obtained while only requiring an energy input of 1.10 kWh/kg.

While extracellular vesicles (EVs) are established mediators of intra-species signaling, their contribution to cross-kingdom communication remains incompletely understood. Here, we investigate the EV-mediated interactions between human colon epithelial cells and both Gram-positive and Gram-negative gut bacteria. We show that bacterial EVs (BEVs) derived from Lacticaseibacillus casei, Enterococcus faecalis, and Proteus mirabilis induce distinct transcriptomic changes in Caco-2 cells depending on the bacterial species, with up to ~6,000 differentially expressed genes, including CCL20, CXCL8, or CXCL10. Transfection of BEV-derived RNA independently induces a subset of similar effects, indicating that the EV-mediated communication is partially driven by the RNA cargo. Conversely, we demonstrate that bacteria interact with Caco-2-derived EVs and miR-192-5p, which is highly abundant (~36.4-fold higher) in EVs isolated from conditioned medium compared with EVs from unconditioned medium, with modest effects on bacterial growth. Furthermore, we show that lipid-based packaging of miR-192-5p modulates its association with the bacteria. Our findings support a conceptual model in which EVs and their RNA cargo contribute to species-dependent host-microbe interactions. This study introduces a framework for understanding EVs as cross-kingdom regulators and underscores the importance of tailored, context-specific analyses for understanding the scope of EV-mediated interactions in microbiome-host homeostasis and disease.

The formation of a stable cathode-electrolyte interphase (CEI) is critical for the performance of lithium–sulfur (Li–S) batteries with carbonate-based electrolytes, as it suppresses parasitic polysulfide reactions and enables solid-state sulfur conversion. In nanoporous carbon hosts, the CEI together with nanopore confinement plays a key role in capacity retention and long-term cycling. Yet, its spatial formation, stability, and contribution to electrochemical performance remain poorly understood, partly due to challenges in characterization caused by beam and air sensitivity. Here, we employ cryogenic transmission electron microscopy (cryo-TEM) with electron energy loss spectroscopy and energy-dispersive X-ray spectroscopy, X-ray photoelectron spectroscopy and electrochemical testing together with galvanostatic intermittent titration technique measurements to elucidate how carbon particle size affects CEI formation and electrochemical performance. We find that the CEI is not a uniform surface film but extends heterogeneously into the particle bulk. Mass transport during the first discharge dictates CEI development, and larger particles suffer from inactive regions due to the preferential CEI formation only in the outer regions of the particles. During extended cycling, charge transfer resistance at confined CEI/active material/carbon interfaces emerges as the dominant performance-limiting factor. These findings show that particle size controls CEI formation during initial discharge, offering guidance for designing carbon hosts from nano- to micrometer length scales in Li–S battery cathodes.