ERK activation waves coordinate mechanical cell competition leading to collective elimination via extrusion of bacterially infected cells.

Epithelial cells respond to infection with the intracellular bacterial pathogen Listeria monocytogenes by altering their mechanics to promote collective infected cell extrusion (CICE) and limit infection spread across cell monolayers. However, the underlying biochemical pathways remain elusive. Here, using in vitro (epithelial monolayers) and in vivo (zebrafish larvae) models of infection with L.

StretchView - A Multi-Axial Cell-Stretching Device for Long-Term Automated Videomicroscopy of Living Cells.

Incorporating mechanical stretching of cells in tissue culture is crucial for mimicking (patho)-physiological conditions and understanding the mechanobiological responses of cells, which can have significant implications in areas like tissue engineering and regenerative medicine. Despite the growing interest, most available cell-stretching devices are not compatible with automated live-cell imaging, indispensable for characterizing alterations in the dynamics of various important cellular processes. In this work, StretchView is presented, a multi-axial cell-stretching platform compatible with automated, time-resolved live-cell imaging.

Evaluating the Potential of Microdroplet Flow in Two-Phase Biocatalysis: A Systematic Study.

Two-phase biocatalysis in batch reactions often suffers from inefficient mass transfer, inconsistent reaction conditions, and enzyme inactivation issues. Microfluidics offer uniform and controlled environments ensuring better reproducibility and enable efficient, parallel processing of many small-scale reactions, making biocatalysis more scalable. In particular, the use of microfluidic droplets can increase the interfacial area between the two phases and can therefore also increase reaction rates.

Biocatalytic Ether Lipid Synthesis by an Archaeal Glycerolprenylase.

Although ethers are common in secondary natural products, they are an underrepresented functional group in primary metabolism. As such, there are comparably few enzymes capable of constructing ether bonds in a general fashion. However, such enzymes are highly sought after for synthetic applications as they typically operate with higher regioselectivity and under milder conditions than traditional organochemical approaches.

2PP-Hydrogel Covered Electrodes to Compensate for Media Effects in the Determination of Biomass in a Capillary Wave Micro Bioreactor.

Microbioreactors increase information output in biopharmaceutical screening applications because they can be operated in parallel without consuming large quantities of the pharmaceutical formulations being tested. A capillary wave microbioreactor (cwMBR) has recently been reported, allowing cost-efficient parallelization in an array that can be activated for mixing as a whole. Although impedance spectroscopy can directly distinguish between dead and viable cells, the monitoring of cells in suspension within bioreactors is challenging because the signal is influenced by the potentially varying properties of the culture medium.

Substrate-Based Ligand Design for Phenazine Biosynthesis Enzyme PhzF.

The phenazine pyocyanin is an important virulence factor of the pathogen Pseudomonas aeruginosa, which is on the WHO list of antibiotic resistant "priority pathogens". In this study the isomerase PhzF, a key bacterial enzyme of the pyocyanin biosynthetic pathway, was investigated as a pathoblocker target. The aim of the pathoblocker strategy is to reduce the virulence of the pathogen without killing it, thus preventing the rapid development of resistance.

A High-Aspect-Ratio Deterministic Lateral Displacement Array for High-Throughput Fractionation.

Future industrial applications of microparticle fractionation with deterministic lateral displacement (DLD) devices are hindered by exceedingly low throughput rates. To enable the necessary high-volume flows, high flow velocities as well as high aspect ratios in DLD devices have to be investigated. However, no experimental studies have yet been conducted on the fractionation of bi-disperse suspensions containing particles below 10 µm with DLD at a Reynolds number (Re) above 60.

Effect of particle size on the dispersion behavior of magnesium stearate blended with microcrystalline cellulose.

The majority of tablets manufactured contain lubricants to reduce friction during ejection. However, especially for plastically deforming materials, e.g.

Investigation of Dispersion Kinetics of Particulate Lubricants and their Effect on the Mechanical Strength of MCC Tablets.

Introduction: Tablets are commonly produced by internally adding particulate lubricants, which are known to possibly lower the mechanical strength of tablets. This reduction is caused by the coverage of matrix forming components by lubricant particles, resulting in decreased interparticulate interactions. The known incompatibilities with some active compounds of the predominantly used lubricant, magnesium stearate, call for the in-depth characterization of alternative lubricants.

Performance of cross-linked enzyme crystals of engineered halohydrin dehalogenase HheG in different chemical reactor systems.

Halohydrin dehalogenase HheG is an industrially interesting biocatalyst for the preparation of different β-substituted alcohols starting from bulky internal epoxides. We previously demonstrated that the immobilization of different HheG variants in the form of cross-linked enzyme crystals (CLECs) yielded stable and reusable enzyme immobilizes with increased resistance regarding temperature, pH, and the presence of organic solvents. Now, to further establish their preparative applicability, HheG D114C CLECs cross-linked with bis-maleimidoethane have been successfully produced on a larger scale using a stirred crystallization approach, and their application in different chemical reactor types (stirred tank reactor, fluidized bed reactor, and packed bed reactor) was systematically studied and compared for the ring opening of cyclohexene oxide with azide.

Isolation and Cultivation of Porcine Endothelial Cells, Pericytes and Astrocytes to Develop an In Vitro Blood-Brain Barrier Model for Drug Permeation Testing.

The blood-brain barrier (BBB) is the bottleneck in the development of new drugs to reach the brain. Due to the BBB, toxic substances cannot enter the brain, but promising drug candidates also pass the BBB poorly. Suitable in vitro BBB models are therefore of particular importance during the preclinical development process, as they can not only reduce animal testing but also enable new drugs to be developed more quickly.

Process and formulation parameters influencing the survival of Saccharomyces cerevisiae during spray drying and tableting.

Probiotic microorganisms provide health benefits to the patient when administered in a viable form and in sufficient doses. To ensure this, dry dosage forms are preferred, with tablets in particular being favored due to several advantages. However, the microorganisms must first be dried as gently as possible.

Amyloid-like aggregation of recombinant β-lactoglobulin at pH 3.5 and 7.0: Is disulfide bond removal the key to fibrillation?

Functional nanofibrils from globular proteins are usually formed by heating for several hours at pH 2.0, which induces acidic hydrolysis and consecutive self-association. The functional properties of these micro-metre-long anisotropic structures are promising for biodegradable biomaterials and food applications, but their stability at pH > 2.

Tableting of fluidized bed granules containing living microorganisms.

Tablets are the favored dosage form for numerous active pharmaceutical ingredients, among others because they are easy to take, ensure safe dosing and allow cost-effective production on a large scale. This dosage form is also frequently chosen for the administration of viable probiotic microorganisms. Saccharomyces cerevisiae cells granulated in a fluidized bed process, with dicalcium phosphate (DCP), lactose (LAC) and microcrystalline cellulose (MCC) as carrier materials, were tableted using a compaction simulator, varying the compression stress.

Biosynthesis of polyprenylated xanthones in Hypericum perforatum roots involves 4-prenyltransferase.

Polyprenylated xanthones are natural products with a multitude of biological and pharmacological activities. However, their biosynthetic pathway is not completely understood. In this study, metabolic profiling revealed the presence of 4-prenylated 1,3,5,6-tetrahydroxyxanthone derivatives in St.

Enhanced multi-component model to consider the lubricant effect on compressibility and compactibility.

Modeling of structural and mechanical tablet properties consisting of multiple components, based on a minimum of experimental data is of high interest, in order to minimize time- and cost-intensive experimental trials in the development of new tablet formulations. The majority of commonly available models use the compressibility and compactibility of constituent components and establish mixing rules between those components, in order to predict the tablet properties of formulations containing multiple components. However, their applicability is limited to single materials, which form intact tablets (e.

Integration of Extracellular Matrices into Organ-on-Chip Systems.

The extracellular matrix (ECM) is a complex, dynamic network present within all tissues and organs that not only acts as a mechanical support and anchorage point but can also direct fundamental cell behavior, function, and characteristics. Although the importance of the ECM is well established, the integration of well-controlled ECMs into Organ-on-Chip (OoC) platforms remains challenging and the methods to modulate and assess ECM properties on OoCs remain underdeveloped. In this review, current state-of-the-art design and assessment of in vitro ECM environments is discussed with a focus on their integration into OoCs.

The Effect of Particle Shape on the Compaction of Realistic Non-Spherical Particles-A Multi-Contact DEM Study.

The purpose of this study was to investigate the deformation behavior of non-spherical particles during high-load compaction using the multi-contact discrete element method (MC-DEM). To account for non-spherical particles, the bonded multi-sphere method (BMS), which incorporates intragranular bonds between particles, and the conventional multi-sphere (CMS), where overlaps between particles are allowed to form a rigid body, were used. Several test cases were performed to justify the conclusions of this study.

Effect of Process Parameters, Protectants and Carrier Materials on the Survival of Yeast Cells during Fluidized Bed Granulation for Tableting.

The administration of living microorganisms is of special interest, with regard to probiotic microorganisms providing health benefits to the patient. Effective dosage forms require the preservation of microbial viability until administration. Storage stability can be improved by drying, and the tablet is an especially attractive final solid dosage form due to its ease of administration and its good patient compliance.

Low-Cost Impedance Camera for Cell Distribution Monitoring.

Electrical impedance spectroscopy (EIS) is widely recognized as a powerful tool in biomedical research. For example, it allows detection and monitoring of diseases, measuring of cell density in bioreactors, and characterizing the permeability of tight junctions in barrier-forming tissue models. However, with single-channel measurement systems, only integral information is obtained without spatial resolution.

Understanding adsorption behavior of antiviral labyrinthopeptin peptides in anion exchange chromatography.

Lantipeptides from bacterial sources are increasingly important as biopharmaceuticals because of their broad range of applications. However, the availability of most lantipeptides is low, and systematic approaches for downstream processing of this group of peptides is still lacking. Model-based development for chromatographic separations has proven to be a useful tool for developing reliable purification processes.

Cell-stretching devices: advances and challenges in biomedical research and live-cell imaging.

Basic human functions such as breathing and digestion require mechanical stretching of cells and tissues. However, when it comes to laboratory experiments, the mechanical stretching that cells experience in the body is not often replicated, limiting the biomimetic nature of the studies and the relevance of results. Herein, we establish the importance of mechanical stretching during in vitro investigations by reviewing seminal works performed using cell-stretching platforms, highlighting important outcomes of these works as well as the engineering characteristics of the platforms used.

Production of benzylglucosinolate in genetically engineered carrot suspension cultures.

Glucosinolates, a group of sulfur-containing specialized metabolites of the Brassicales, have attracted a lot of interest in nutrition, medicine and agriculture due to their positive health effects and their involvement in plant defense. Their biological activities and the extensive knowledge of their biosynthesis have inspired research into development of crops with enhanced glucosinolate contents as well as their biotechnological production in homologous and heterologous systems. Here, we provide proof-of-concept for transgenic suspension cultures of carrot (, Apiacae) as a scalable production platform for plant specialized metabolites using benzylglucosinolate as a model.