INMdok (Leibniz Institute for New Materials)
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Should you hire new searchers? Optimal number of agents in a collective search, and when to launch them
Search processes often involve multiple agents that collectively look for a randomly located target. While increasing the number of agents usually decreases the time at which the first agent finds the target, it also requires resources to create and sustain more agents. In this letter, we consider a collective search cost that not only accounts for the search time but also for the cost associated to the creation and the maintenance of an agent. We first present a general formalism for independent agents in terms of the survival probability of the target for a single-agent search s(t), where we allow agents to be introduced in the system one after the other. From this, we first derive analytically the optimal number of searchers to launch initially in the system. Then, we identify the optimal strategies for exponential and algebraic single-agent survival probabilities by pointing out the ideal times at which new searchers should be launched in the system. Our results show that all searchers should be launched simultaneously in the exponential case, while some should be launched at later times in the algebraic case. Finally, we compare these results with numerical simulations of a strongly interacting collective search, the true self-avoiding walk, and show how the optimal strategy differ from the non-interacting case
T cell polarization and NFAT translocation are stiffness-dependent and are differentially regulated by Piezo1 and Orai1
Effective T cell responses against tumor cells require diverse effector functions including polarization towards tumor cells to form immunological synapses and nuclear factor of activated T-cells (NFAT)-dependent gene transcription. While the role of tumor cell softening has been associated with malignancy, stemness, and metastasis, potentially contributing to immune evasion, its impact on cellular processes in T cells is not well understood. Here, we show that both T cell polarization and NFAT nuclear translocation are modulated by target stiffness in a Ca2+ dependent manner. Using both anti-CD3 antibody-functionalized substrates with varying stiffness as surrogates for target cells or softened tumor cells, we found that both, reorientation of microtubule organizing center (MTOC) towards the tumor cells, a hallmark for T cell polarization, and NFAT translocation were impaired on softer hydrogels or following contact with softer cancer cells. The amplitudes of intracellular Ca2+ signals were dependent on stiffness, and removal of extracellular Ca2+ inhibited stiffness-dependent T cell responsiveness. While stiffness-dependent Ca2+ signaling was crucial for both, T cell polarization and NFAT translocation, Ca2+ influx through Piezo1, a mechanosensitive ion channel, mediated stiffness-dependent MTOC reorientation but not NFAT translocation. In contrast, Ca2+ influx through store-operated Orai channels mediated NFAT translocation but not MTOC reorientation. Our results demonstrate that tumor cell stiffness directly influences T cell functionality through distinct Ca2+ influx pathways, revealing cell softening as an essential mechanism employed by malignant cells to evade immune surveillance
Recyclable in-mold and printed electronics with polymer separation layers
Recycling of Waste from Electrical and Electronic Equipment (WEEE) is crucial in preventing resource depletion and promoting a circular economy. The increasing fraction of printed and in-mold electronics is particularly challenging. The combinations of polymers and printed metals are difficult to disassemble due to the strong interfaces that are formed to create reliable in-mold devices. The relatively low metal content makes recycling uneconomical and those valuable materials are then lost to landfill or incineration. Separation layers enable design-for-recycling with minimal modifications during the fabrication process, while preserving product performance and reliability. We present a scalable method for preparing polymer separation layers for printed and in-mold electronics. Slot-die coating is used to prepare water-soluble polymer films with a dry thickness of less than 10 μm on commodity polymer substrates. This separation layer improves the bending stability of inkjet- and screen-printed circuits. Furthermore, it is compatible with typical polymer processing methods, such as thermoforming and injection molding. Various methods, including plasma treatment, are presented to ensure adhesion of the modified interfaces. Finally, we investigate the material recovery and demonstrate the release of the integrated metal within a few minutes by dissolving the separation layer in water. This material recovery process can be readily integrated into current WEEE recycling processes
Hyaluronic Acid-based Inks for Stereolithography (Bio)printing: Benefits of Thiol-ene vs. Acrylate Functionalized Inks
Hydrogel inks used for 3D bioprinting are mainly based on radical polymerization of methacrylate groups. Inks based on the radical thiol-ene polymerization have raised attention in recent years, as they are not susceptible to oxygen inhibition and require lower light doses for polymerization, therefore, they can be more benign to living cells. Here, we modified hyaluronic acid inks with allyl ether or norbornene groups, which can form a crosslinked network in the presence of a dithiol crosslinker. We performed systematic studies to compare precursor stability, photocrosslinking and printability of the thiol-ene inks with methacrylated hyaluronic acid inks. Our results showed higher storage stability of the thiol-ene hydrogel precursors over 15 months. Photorheology experiments demonstrated faster photocrosslinking and higher temporal control over the network formation in thiol-ene inks. The suitability of thiol-ene inks was demonstrated using digital light processing-based printing with a minimum print time of 2 s per layer and a xy resolution of 100 µm
Near-Infinite-Chain Polymers with Ge=Ge Double Bonds
Despite considerable interest in heteroatom-containing conjugated polymers, there are only few examples with heavier p-block elements in the conjugation path. The recently reported heavier acyclic diene metathesis (HADMET) allowed for the synthesis of a polymer containing Ge=Ge double bonds—albeit insoluble and with limited degree of polymerization. By incorporation of long alkyl chains, we now obtained soluble representatives, which exhibit degrees of polymerization near infinity according to diffusion-ordered NMR spectroscopy (DOSY) and dynamic light scattering (DLS). UV/Vis and NMR data confirm the presence of σ,π-conjugation across the silylene-phenylene linkers between the Ge=Ge double bonds. Favorable intermolecular dispersion interactions lead to ladder-like cylindrical assemblies as confirmed by X-ray diffraction (XRD), small angle X-ray scattering (SAXS) and DLS. AFM and TEM images of deposited thin films reveal lamellar ordering of extended polymer bundles
Thermo-amplifier circuit in probiotic E. coli for stringently temperature-controlled release of a novel antibiotic
Peptide drugs have seen rapid advancement in biopharmaceutical development, with over 80 candidates approved globally. Despite their therapeutic potential, the clinical translation of peptide drugs is hampered by challenges in production yields and stability. Engineered bacterial therapeutics is a unique approach being explored to overcome these issues by using bacteria to produce and deliver therapeutic compounds at the body site of use. A key advantage of this technology is the possibility to control drug delivery within the body in real time using genetic switches. However, the performance of such genetic switches suffers when used to control drugs that require post-translational modifications or are toxic to the host. In this study, these challenges were experienced when attempting to establish a thermal switch for the production of a ribosomally synthesized and post-translationally modified peptide antibiotic, darobactin, in probiotic E. coli. These challenges were overcome by developing a thermo-amplifier circuit that combined the thermal-switch with a T7 RNA Polymerase and its promoter that overcame limitations imposed by the host transcriptional machinery due to its orthogonality to it. This circuit enabled production of pathogen-inhibitory levels of darobactin at 40°C while maintaining leakiness below the detection limit at 37°C. More impressively, the thermo-amplifier circuit sustained production beyond the thermal induction duration. Thus, raised temperature for 2 h was sufficient for the bacteria to produce pathogen-inhibitory levels of darobactin even in the physiologically relevant simulated conditions of the intestines that include bile salts and low nutrient levels
Friction Perception on Fine and Coarse Textured Surfaces
Fingertip friction plays a key role in tactile interactions, but the perception of friction in active touch has rarely been studied. In this psychophysical study, we examine the impact of feature sizes on micro-structured surfaces on friction perception. First results indicate that the perception of friction differences is deteriorated when a surface with structures smaller than 100 µm is compared with larger structures, possibly in agreement with the two pathways proposed in Katz’ duplex theory of tactile perception
High-Performance Lithium-Ion Batteries with High Stability Derived from Titanium-Oxide- and Sulfur-Loaded Carbon Spherogels
This study presents a novel approach to developing high-performance lithium-ion battery electrodes by loading titania-carbon hybrid spherogels with sulfur. The resulting hybrid materials combine high charge storage capacity, electrical conductivity, and core-shell morphology, enabling the development of next-generation battery electrodes. We obtained homogeneous carbon spheres caging crystalline titania particles and sulfur using a template-assisted sol-gel route and carefully treated the titania-loaded carbon spherogels with hydrogen sulfide. The carbon shells maintain their microporous hollow sphere morphology, allowing for efficient sulfur deposition while protecting the titania crystals. By adjusting the sulfur impregnation of the carbon sphere and varying the titania loading, we achieved excellent lithium storage properties by successfully cycling encapsulated sulfur in the sphere while benefiting from the lithiation of titania particles. Without adding a conductive component, the optimized material provided after 150 cycles at a specific current of 250 mA g–1 a specific capacity of 825 mAh g–1 with a Coulombic efficiency of 98%
Rheological behavior of Pluronic/Pluronic diacrylate hydrogels used for bacteria encapsulation in engineered living materials
Pluronic (Plu) hydrogels mixed with variable fractions of Pluronic diacrylate (PluDA) have become popular matrices to encapsulate bacteria and control their growth in engineered living materials. Here we study the rheological response of 30 wt.% Plu/PluDA hydrogels with PluDA fraction between 0 and 1. We quantify the range of viscoelastic properties that can be covered in this system by varying in the PluDA fraction. We present stress relaxation and creep-recovery experiments and describe the variation of the critical yield strain/stress, relaxation and recovery parameters of Plu/PluDA hydrogels as function of the covalent crosslinking degree using the Burgers and Weilbull models. The analyzed hydrogels present two stress relaxations with different timescales which can be tuned with the covalent crosslinking degree. We expect this study to help users of Plu/PluDA hydrogels to estimate the mechanical properties of their systems, and to correlate them with the behaviour of bacteria in future Plu/PluDA devices of similar composition
PIEZO1-mediated mechanosensing governs NK-cell killing efficiency and infiltration in three-dimensional matrices
Natural killer (NK) cells play a vital role in eliminating tumorigenic cells. Efficient locating and killing of target cells in complex three-dimensional (3D) environments are critical for their functions under physiological conditions. However, the role of mechanosensing in regulating NK-cell killing efficiency in physiologically relevant scenarios is poorly understood. Here, we report that the responsiveness of NK cells is regulated by tumor cell stiffness. NK-cell killing efficiency in 3D is impaired against softened tumor cells, whereas it is enhanced against stiffened tumor cells. Notably, the durations required for NK-cell killing and detachment are significantly shortened for stiffened tumor cells. Furthermore, we have identified PIEZO1 as the predominantly expressed mechanosensitive ion channel among the examined candidates in NK cells. Perturbation of PIEZO1 abolishes stiffness-dependent NK-cell responsiveness, significantly impairs the killing efficiency of NK cells in 3D, and substantially reduces NK-cell infiltration into 3D collagen matrices. Conversely, PIEZO1 activation enhances NK killing efficiency as well as infiltration. In conclusion, our findings demonstrate that PIEZO1-mediated mechanosensing is crucial for NK killing functions, highlighting the role of mechanosensing in NK-cell killing efficiency under 3D physiological conditions and the influence of environmental physical cues on NK-cell functions