Scientific publications

Approaches in tissue engineering, organoid culture, and organs-on-chip have propelled the development of increasingly sophisticated in vitro models of human tissues. However, as they are formed from natural cells, it is challenging to control their molecular composition and biophysical properties, increasing variability and limiting their robustness. To overcome these limitations, we introduce a self-assembly strategy for synthetic cells that enables the formation of millimeter-sized synthetic constructs based on single synthetic cells. Specifically, we functionalize the lipid membrane of synthetic cells with cholesterol-tagged single-stranded DNA aptamers, which drive programmable intercellular adhesion through sequence-specific hybridization. This allows individual synthetic cells to interconnect into higher order 3D constructs. By varying aptamer complementarity, internal architecture with spatially distinct functional zones and tuneable mechanical properties can be encoded. Most importantly, the DNA-driven self-assembly operates directly in cell culture medium, is compatible with high-throughput microwell formats enabling scalable screening workflows and is reversible by DNA displacement. To demonstrate the biological functionality of these synthetic tissues, we incorporate T cell-stimulatory antibodies into spatially segregated tissue regions. This design mimics lymph node organization and supports infiltration of natural primary human T cells, which subsequently expand within the synthetic tissue. Together, these results establish a route to tissue-scale matrices built from synthetic cell collectives and represent a critical step toward functionally integrating living and non-living matter.

Special Issue

Our perception does not consist of isolated events but unfold and adapt over time, forming a continuous stream of experience. How we perceive an object is influenced not only by its intrinsic characteristics but also by our recent interactions, leading to sequential effects (i.e., serial dependence). In this study, we investigated whether such effects occur in haptic material perception, specifically in pleasantness and roughness. We also examined whether serial dependence is grounded in the physical object properties or the task at hand (i.e., perceptual attribute). To this end, we used seven sandpaper samples ranging in roughness (18.3 to 425 microns). In two separate sessions, individuals explored the samples with their index finger and rated how pleasant or rough each object feels. Our results revealed a significant attractive serial dependence in roughness judgments and a weaker repulsive serial dependence in pleasantness judgments. This shows distinct patterns of serial dependence for roughness and pleasantness emerging for the same physical stimuli. These divergent patterns for the same stimuli suggest that serial dependence in haptics is attribute dependent, reflecting higher order mechanism rather than being purely driven by stimulus characteristics. Recognizing the role of serial dependence in haptics opens new avenues for haptic interfaces and engineering user experiences.

Conductive polymer composites for printed stretchable temperature sensors must remain functional during many strain cycles despite unavoidable changes in their microstructure and thus the electrically conductive network. In this study, we introduce screen-printable inks with electrical conductivities and temperature coefficients of resistance (TCR, α) that are suitable for application in temperature sensors while retaining thermal and mechanical stability upon stretching the printed sensors. Silver flakes (AgF) and carbon black (CB) or graphite flakes (GR) at different ratios were combined as conductive fillers in dragon skin (DS) elastomer and screen printed. Their electrothermal properties were characterized within the temperature range of 20°C–120°C. Samples with constant α in suitable ranges were selected and characterized electrically for stability during thermal cycling and mechanically during 30 000 strain cycling. The DS-AgF-CB12-180°C and DS-AgF-GR10-180°C composites exhibited linear resistance changes with α = 2.29 × 10−3/°C and 1.75 × 10−3/°C, respectively. The resistance of DS-AgF-GR drifted below 2% over 10 thermal cycling and relative resistance changes (R/R0) increased up to 8 after 30 000 strain cycling at 0%–10%. We show that the carbon particles modify the metal–matrix interactions in the hybrid composites, thus increasing stability and reliability of temperature sensing.

Neutrophils are central first responders in immune defense. They exhibit a remarkable phenotypic and functional plasticity with time- and context-specific properties and activities. Their short lifespan is tightly controlled, with neutrophils surviving hours in circulation before undergoing apoptosis and clearance. Tissue immigration and exposure to the local cytokine microenvironment can significantly expand the lifetime of neutrophils to several days. Various pathological conditions, such as microbial infections, cancers, and other diseases, can modulate the neutrophil lifespan. This can lead to an accumulation of aged neutrophils with specialized phenotypes and modes of action. In this regard, the host-microbe interaction in cancers at body interfaces generates a transkingdom effect on neutrophil lifetime affecting patient survival and treatment susceptibility. Here, we introduce critical modulators of neutrophil survival, including microbe-associated and cancer-related cues, highlighted as hallmarks of neutrophil survival. In this review, we discuss resulting perspectives on the immunotherapeutic potential of neutrophils and the application of engineered IgA antibodies. Integrating these insights into future research efforts could lead to innovative strategies. Targeted programming of neutrophil function will help to increase the efficacy of immunotherapies and improve outcomes in cancer and other neutrophil-associated diseases.

Developing effective vaccines against some diseases remains a global health priority. However, targeting immunity against a specific disease-related antigen requires efficient adjuvant systems that adequately promote vaccination efficacy. Extracellular vesicles have been identified as a potential adjuvant platform technology but are still limited in their reproducibility and safety. Here, we present a synthetic extracellular vesicle mimetic (EVM) platform that enhances antigen immunogenicity by incorporating the large extracellular loop (LEL) of the tetraspanin CD9, a protein abundant on natural extracellular vesicles. Liposomes with defined lipid composition were functionalized with recombinant CD9-LEL and pathogen antigens—KMP-11 from Leishmania and the SARS-CoV-2 Spike (S) protein. BALB/c mice were immunized intraperitoneally with nanovesicles carrying CD9-LEL, the pathogen antigens alone, or both. Antigen-specific IgG responses were measured by ELISA, and vesicle uptake by immune cells was assessed via flow cytometry. CD9-LEL alone did not elicit an immune response, but its co-presentation with antigens significantly enhanced specific anti-pathogen IgG titers. Notably, KMP-11 alone failed to induce detectable antibodies, while nanovesicles carrying both CD9-LEL and KMP-11 triggered strong IgG1 and IgG2b responses. Similarly, nCD9 + S induced higher IgG titers than S alone. CD9-LEL promoted uptake of nanovesicles by peritoneal macrophages, suggesting improved antigen presentation.
Combining EVMs with classical adjuvants further modulated the immune profile: alum favored IgG1 (Th2 bias), while CpG ODNs enhanced IgG2a and IgG2b (Th1 bias), crucial for intracellular pathogen clearance. The platform demonstrated safety and adaptability. In conclusion, CD9-LEL-decorated EVMs represent a promising, scalable vaccine strategy capable of boosting antigen immunogenicity and directing immune polarization, offering a versatile tool for combating challenging or emergent infectious diseases.

We report a hybrid layered metal-phosphonate framework, [Ni(2,2’-bpy)3]2+[(VO(H2O))2(VO)4(μ-O)2(C6H5PO3)6]2–·2H2O, in which redox-active [(Ni(2,2’-bpy)3)]2+ cations are embedded between anionic vanadium phosphonate layers [(VO(H2O))2(VO)4(μ-O)2(C6H5PO3)6]2– (with 2,2’-bpy = 2,2’-bipyridine). X-ray photoelectron spectroscopy reveals coexisting Ni2+, V2+, V3+, and V4+/V5+ species on the surface of the crystals, indicating a highly dynamic redox system. The material exhibits a main photoluminescence peak at 2.25 eV and strong short-range antiferromagnetic coupling between the V4+ centers. Electrochemical characterization in aqueous media yields capacitances of 79 F/g in Na2SO4 (pH 7) and 43 F/g in H3PO4 (pH 4) at 1 A/g. In Na2SO4 (pH 7), the material reaches about 300 F/g at a scan rate of 1 mV/s and retains capacity over more than 10,000 cycles. The crystals remain chemically stable between pH 2 and pH 10 for at least 1 week. Combined sustainable synthesis, robust redox activity, high capacitance, long cycle stability, and broad pH tolerance make these hybrid metal-phosphonate crystals promising candidates for next-generation aqueous energy-storage applications.

Combinations of two different colloidal nanostructures can inherit properties of both and give access to new, emerging properties. Here, we create optically downconverting heteroaggregates of carbon quantum dots and lanthanide doped nanocrystals with high quantum yields and stability against blinking and bleaching. These heteroaggregates are heavy metal-free and display visible emissions that are suitable for multimodal sensing. Red emitting europium Eu3+ doped CaF2 nanoparticles were combined with orange emitting carbon quantum dots prepared by solvothermal reactions. Simple mixing led to the formation of heteroaggregates as confirmed by dynamic light scattering and zeta potential analysis. The assembly caused electromagnetic coupling, changed the particles' response to temperature and pH in aqueous dispersion, and increased the sensing performance. Emission dropped by 39% at 550 nm (of carbon quantum dots) and 8% at 613 nm (of Eu3+ doped CaF2 nanocrystals) from 17% and 33% of the pure nanoparticle dispersions. Changing pH from 1.3 to 12.5 quenched emissions by 92% and 74% at the same wavelengths, increasing from 62% and 47% of the pure dispersions. Ratiometric calibrations based on the intensity ratio of the 550 nm and 613 nm emissions were constructed to use the heteroaggregates as sensors. They performed as optical thermometers in the range from 293 K to 333 K with a temperature resolution of 0.35 K, and pH values within a range from 1.3 to 12.5 with a resolution of 0.15 pH units. Our results show that heteroaggregates of coupled nanostructures provide improved performance in temperature and pH sensing.

Salts induce the agglomeration and assembly of gold nanocrystals that are stabilized by charged ligand shells. This destabilization is known to partially deviate from the predictions of classical DLVO theory for larger colloids, but existing studies focus on limited concentration ranges or ion types. Here, we use a high-throughput approach to test the agglomeration efficacy of 17 different salts at concentrations ranging from 0.16 mM to 2 M on negatively charged nanocrystals with shells of 11-mercaptoundecanoic acid and/or triethylene glycol mono-11-mercaptoundecyl ether. Automated pipetting is used to create a large dataset of close to 10000 UV–vis absorbance spectra. We analyze the spectral shifts to find the onset of agglomeration, identify critical salt concentrations, and characterize the nature of the agglomeration transition. The results are compared to classical DLVO theory using conventional analysis, and the effects of ion concentration and anion valency are shown to be consistent with DLVO predictions. Cation valencies only partially follow the predictions, suggesting local ion-specific interactions that dominate when screening lengths reach molecular length scales. A Random Forest Regression model is used as additional “black box” analysis of the results to correlate the ionic strength, ligand shell composition, and intrinsic ion properties, and to rank their relative importance to the colloidal stability of gold nanocrystals. The ranking combines classical DLVO effects and specific ion interactions with subtle effects on the agglomerate structure that affect plasmon resonance shifts, providing a complementary interpretation of the data.

Abstract Skin physiology varies greatly between anatomical locations, with impact on tactile
sensitivity. Research on the variations in morphology and physiology between different anatomical
locations of glabrous skin is limited so far. This study investigates the morphology and physiology
of glabrous skin on the human hand (N = 60), including the index finger pads of dominant and
non-dominant hand, the small finger pads, the thenar palm and the volar arm as hairy skin reference.
We employed laser scanning microscopy, optical coherence tomography, skin corneometry, skin
cutometry and two-point discrimination measurements as non-invasive in situ methods. We found
significant morphological and physiological differences between fingers, palm and volar arm. The
finger pads had a thicker stratum corneum (SC), especially the index finger of the dominant hand.
They also exhibited higher skin hydration and a higher density of Meissner corpuscles and of
sweat glands compared to the palm. All parameters exhibited strong interindividual variability.
A correlation between anatomical positions for individuals was found for some but not all
parameters. The skin’s mechanical response differed significantly between the anatomical locations,
in correlation with skin hydration for all glabrous skin positions. The effect of ageing on skin elasticity
was strongest on the hairy skin of the volar arm. In glabrous skin ageing affected the density of
Meissner corpuscles and thus spatial acuity. Glabrous skin exhibits a high specialization depending
on the anatomical position. Physiological and morphological parameters play a crucial role in its
mechanical properties and tactile acuity.