Publikationen

Current environmental challenges and the shrinking fossil-fuel feedstock are important criteria for the next generation of polymer materials. In this context, we present a fully bio-based material, which shows promise as a thermoplastic elastomer (TPE). Due to the use of β-farnesene and L-lactide as monomers, bio-based feedstocks, namely sugar cane and corn, can be used. A bifunctional initiator for the carbanionic polymerization was employed, to permit an efficient synthesis of ABA-type block structures. In addition, the “green” solvent MTBE (methyl tert-butyl ether) was used for the anionic polymerisation, enabling excellent solubility of the bifunctional anionic initiator. This afforded low dispersity (Đ=1.07 to 1.10) and telechelic polyfarnesene macroinitiators. These were employed for lactide polymerization to obtain H-shaped triblock copolymers. TEM and SAXS revealed clearly phase-separated morphologies, and tensile tests demonstrated elastic mechanical properties. The materials featured two glass transition temperatures, at – 66 °C and 51 °C as well as gyroid or cylindrical morphologies, resulting in soft elastic materials at room temperature.

There are no targeted therapies for patients with triple-negative breast cancer (TNBC). TNBC is enriched in breast cancer stem cells (BCSC), which play a key role in metastasis, chemoresistance, relapse, and mortality. γδ T cells hold great potential in immunotherapy against cancer and might provide an approach to therapeutically target TNBC. γδ T cells are commonly observed to infiltrate solid tumors and have an extensive repertoire of tumor-sensing mechanisms, recognizing stress-induced molecules and phosphoantigens (pAgs) on transformed cells. Herein, we show that patient-derived triple-negative BCSCs are efficiently recognized and killed by ex vivo expanded γδ T cells from healthy donors. Orthotopically xenografted BCSCs, however, were refractory to γδ T-cell immunotherapy. We unraveled concerted differentiation and immune escape mechanisms: xenografted BCSCs lost stemness, expression of γδ T-cell ligands, adhesion molecules, and pAgs, thereby evading immune recognition by γδ T cells. Indeed, neither promigratory engineered γδ T cells, nor anti–PD-1 checkpoint blockade, significantly prolonged overall survival of tumor-bearing mice. BCSC immune escape was independent of the immune pressure exerted by the γδ T cells and could be pharmacologically reverted by zoledronate or IFNα treatment. These results pave the way for novel combinatorial immunotherapies for TNBC.

The cathode material NaFePO of sodium-ion batteries exhibits complex phase segregation thermodynamics with the existence of an intermediate phase, and large volume change during (dis)charging. A virtual multiscale modeling chain is established to construct a 3D anisotropic electro-chemo-mechanical phase-field model based on first-principles calculations for NaFePO, which considers phase changes, electrochemical reactions, anisotropic diffusion, anisotropic misfit strain, and anisotropic elasticity, as well as the concentration-dependence of the elasticity tensor. The elastic properties of NaFePO are determined by first-principles for the first time. We investigate how surface reaction kinetics and crystal anisotropy influence the full 3D microstructure evolution, with results that include phase evolution, interface morphology, and stress evolution in NaFePO particles. We find that the existence of 1D Na diffusion channels leads to a kinetically arrested state of single wave propagation along [010]. Furthermore, defect-actuated in-plane diffusion induces low-energy single wave propagation along [100] controlled by the concentration dependent anisotropic elasticity tensor. In addition, the morphology of the double wave propagation along [010] is more prone to particle cracking and mechanical degradation. Beyond NaFePO, the findings of this work point towards opportunities to engineer desired phase behavior with better mechanical stability by defect-actuated out-of-1D diffusion of an intercalation electrode material.

Understanding cells' response to the macroscopic and nanoscale properties of biomaterials requires studies in model systems with the possibility to tailor their mechanical properties and different length scales. Here, we describe an interpenetrating network (IPN) design based on a stiff PEGDA host network interlaced within a soft 4-arm PEG-Maleimide/thiol (guest) network. We quantify the nano- and bulk mechanical behavior of the IPN and the single network hydrogels by single-molecule force spectroscopy and rheological measurements. The IPN presents different mechanical cues at the molecular scale, depending on which network is linked to the probe, but the same mechanical properties at the macroscopic length scale as the individual host network. Cells attached to the interpenetrating (guest) network of the IPN or to the single network (SN) PEGDA hydrogel modified with RGD adhesive ligands showed comparable attachment and spreading areas, but cells attached to the guest network of the IPN, with lower molecular stiffness, showed a larger number and size of focal adhesion complexes and a higher concentration of the Hippo pathway effector Yes-associated protein (YAP) than cells linked to the PEGDA single network. The observations indicate that cell adhesion to the IPN hydrogel through the network with lower molecular stiffness proceeds effectively as if a higher ligand density is offered. We claim that IPNs can be used to decipher how changes in ECM design and connectivity at the local scale affect the fate of cells cultured on biomaterials.

Engineered living materials (ELMs) are a new class of materials in which living organism incorporated into diffusive matrices uptake a fundamental role in material's composition and function. Understanding how the spatial confinement in 3D can regulate the behavior of the embedded cells is crucial to design and predict ELM's function, minimize their environmental impact and facilitate their translation into applied materials. This study investigates the growth and metabolic activity of bacteria within an associative hydrogel network (Pluronic-based) with mechanical properties that can be tuned by introducing a variable degree of acrylate crosslinks. Individual bacteria distributed in the hydrogel matrix at low density form functional colonies whose size is controlled by the extent of permanent crosslinks. With increasing stiffness and elastic response to deformation of the matrix, a decrease in colony volumes and an increase in their sphericity are observed. Protein production follows a different pattern with higher production yields occurring in networks with intermediate permanent crosslinking degrees. These results demonstrate that matrix design can be used to control and regulate the composition and function of ELMs containing microorganisms. Interestingly, design parameters for matrices to regulate bacteria behavior show similarities to those elucidated for 3D culture of mammalian cells.

The permeability of the human trabecular meshwork (HTM) regulates eye pressure via a porosity gradient across its thickness modulated by stacked layers of matrix fibrils and cells. Changes in HTM porosity are associated with increases in intraocular pressure and the progress of diseases such as glaucoma. Engineered HTMs could help to understand the structure–function relation in natural tissues and lead to new regenerative solutions. Here, melt electrowriting (MEW) is explored as a biofabrication technique to produce fibrillar, porous scaffolds that mimic the multilayer, gradient structure of native HTM. Poly(caprolactone) constructs with a height of 125–500 μm and fiber diameters of 10–12 μm are printed. Scaffolds with a tensile modulus between 5.6 and 13 MPa and a static compression modulus in the range of 6–360 kPa are obtained by varying the scaffold design, that is, the density and orientation of the fibers and number of stacked layers. Primary HTM cells attach to the scaffolds, proliferate, and form a confluent layer within 8–14 days, depending on the scaffold design. High cell viability and cell morphology close to that in the native tissue are observed. The present work demonstrates the utility of MEW for reconstructing complex morphological features of natural tissues.

Using 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.

Abstract The touching of fibrillar surfaces elicits a broad range of affective reactions, which range from the adverse stinginess of a stiff bristle brush to the pleasant feel of velvet. To study the tactile perception of model fibrillar surfaces, a unique set of samples carrying dense, regular arrays of cylindrical microfibrils with high aspect ratio made from different elastomer materials have been created. Fibril length and material compliance are varied independently such that their respective influence on tactile perception can be elucidated. This work finds that the tactile perception of similarity between samples is dominated by bending of the fibrils under sliding touch. The results demonstrate that variations of material stiffness and of surface structure are not necessarily perceived independently by touch. In the case of fibrillar elastomer surfaces, it is rather the ratio of fibril length and storage modulus which determines fibril bending and becomes the dominant tactile dimension. Visual access to the sample during tactile exploration improves the tactile perception of fibril bendability. Experiments with colored samples show a distraction by color in participants’ decisions regarding tactile similarity only for yellow samples of outstanding brightness.

Self-assembly of nanoscale structures at liquid-solid interfaces occurs in a broad range of industrial processes and is found in various phenomena in nature. Conventional theory assumes spherical particles and homogeneous surfaces, but that model is oversimplified, and nanoscale in-situ observations are needed for a more complete understanding. We used liquid phase scanning transmission electron microscopy (LP-STEM) to examine the interactions that direct the self-assembly of superlattices formed by gold nanoparticles (AuNPs) in non-polar liquids. Varying the molecular coating of the substrate modulated short-ranged attraction and led to switching between a range of different geometric structures including hexagonal close-packed (hcp), simple hexagonal (sh), dodecahedral quasi-crystal (dqc), and body-centered cubic (bcc) lattices, as well as random distributions. Langevin dynamics simulations explain the experimental results in terms of the interplay between nanoparticle faceting, ligand shell structure, and substrate-NP-interactions.