Multipolar Reactive DPD: A Novel Tool for Spatially Resolved Systems Biology

This article reports about a novel extension of dissipative particle dynamics (DPD) that allows the study of the collective dynamics of complex chemical and structural systems in a spatially resolved manner with a combinatorially complex variety of different system constituents. We show that introducing multipolar interactions between particles leads to extended membrane structures emerging in a self-organized manner and exhibiting both the necessary mechanical stability for transport and fluidity so as to provide a two-dimensional self-organizing dynamic reaction environment for kinetic studies in the context of cell biology. We further show that the emergent dynamics of extended membrane bound objects is in accordance with scaling laws imposed by physics.Comment: submitted to CMSB 0

Velocity-space sensitivity of the time-of-flight neutron spectrometer at JET

The velocity-space sensitivities of fast-ion diagnostics are often described by so-called weight functions. Recently, we formulated weight functions showing the velocity-space sensitivity of the often dominant beam-target part of neutron energy spectra. These weight functions for neutron emission spectrometry (NES) are independent of the particular NES diagnostic. Here we apply these NES weight functions to the time-of-flight spectrometer TOFOR at JET. By taking the instrumental response function of TOFOR into account, we calculate time-of-flight NES weight functions that enable us to directly determine the velocity-space sensitivity of a given part of a measured time-of-flight spectrum from TOFOR

Relationship of edge localized mode burst times with divertor flux loop signal phase in JET

A phase relationship is identified between sequential edge localized modes (ELMs) occurrence times in a set of H-mode tokamak plasmas to the voltage measured in full flux azimuthal loops in the divertor region. We focus on plasmas in the Joint European Torus where a steady H-mode is sustained over several seconds, during which ELMs are observed in the Be II emission at the divertor. The ELMs analysed arise from intrinsic ELMing, in that there is no deliberate intent to control the ELMing process by external means. We use ELM timings derived from the Be II signal to perform direct time domain analysis of the full flux loop VLD2 and VLD3 signals, which provide a high cadence global measurement proportional to the voltage induced by changes in poloidal magnetic flux. Specifically, we examine how the time interval between pairs of successive ELMs is linked to the time-evolving phase of the full flux loop signals. Each ELM produces a clear early pulse in the full flux loop signals, whose peak time is used to condition our analysis. The arrival time of the following ELM, relative to this pulse, is found to fall into one of two categories: (i) prompt ELMs, which are directly paced by the initial response seen in the flux loop signals; and (ii) all other ELMs, which occur after the initial response of the full flux loop signals has decayed in amplitude. The times at which ELMs in category (ii) occur, relative to the first ELM of the pair, are clustered at times when the instantaneous phase of the full flux loop signal is close to its value at the time of the first ELM

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Shape recognition of microbial cells by colloidal cell imprints

We have engineered a class of colloids which can recognize the shape and size of targeted microbial cells and selectively bind to their surfaces. These imprinted colloid particles, which we called "colloid antibodies", were fabricated by partial fragmentation of silica shells obtained by templating the targeted microbial cells. We successfully demonstrated the shape and size recognition between such colloidal imprints and matching microbial cells. High percentage of binding events of colloidal imprints with the size matching target particles was achieved. We demonstrated selective binding of colloidal imprints to target microbial cells in a binary mixture of cells of different shapes and sizes, which also resulted in high binding selectivity. We explored the role of the electrostatic interactions between the target cells and their colloid imprints by pre-coating both of them with polyelectrolytes. Selective binding occurred predominantly in the case of opposite surface charges of the colloid cell imprint and the targeted cells. The mechanism of the recognition is based on the amplification of the surface adhesion in the case of shape and size match due to the increased contact area between the target cell and the colloidal imprint. We also tested the selective binding for colloid imprints of particles of fixed shape and varying sizes. The concept of cell recognition by colloid imprints could be used for development of colloid antibodies for shape-selective binding of microbes. Such colloid antibodies could be additionally functionalized with surface groups to enhance their binding efficiency to cells of specific shape and deliver a drug payload directly to their surface or allow them to be manipulated using external fields. They could benefit the pharmaceutical industry in developing selective antimicrobial therapies and formulations

Scaffold free fabrication of linear multicellular assemblies by dielectrophoretic hydrogel trapping technique

We have designed a scaffold-free cell assembly method which can produce linear structures of individual living cells without using templates. The method involves dielectrophoretic assembly of cells suspended in a solution of a gelling agent above the gelling temperature. After the cell assembly in string-like structures was achieved with the AC electric field still applied, we gelled the solution by cooling it below its gelling point. The hydrogel entraps the assembled cell structure, preventing its disassembly and allowing further analysis without the presence of the external electric field. We pre-functionalised the cells with polyelectrolytes before the dielectrophoretic assembly which allowed us to line them up in multicellular strings and bind them together with oppositely charged polyelectrolyte after the gel formation. Finally, by dissolving the hydrogel, we released the linear chains of living cells which were collected and studied by optical and fluorescence microscopy. Cell viability tests with fluorescein diacetate confirmed that the cells in the formed worm-like structures remain viable after the cell assembly procedure. The linear cell aggregates are stable without the electric field and can be further cultured or treated with additional polyelectrolytes which make the method attractive for tissue engineering. We envisage that this technique could find possible applications for assembly of neuron cells in linear structures and more complex cell networks

Triggered release kinetics of living cells from composite microcapsules

We have developed a theoretical model for the kinetics of release of living cells from composite shellac-cell microcapsules. The model describes the kinetics of cell release from the microcapsules triggered by: (i) pH change, which dissolves the shellac and (ii) the growth of the encapsulated cells, when placed in culture media. For pH triggered release of cells from the composite microcapsules, the rate constant of cell release depends on the swelling/dissolution rate of the shellac matrix and varies with the pH of the aqueous media. The model links the microcapsules disintegration time with the cell release rate constant. For growth triggered release of cells from the composite microcapsules, the cell release rate constant depends on concentration of nutrients in the culture media and the volume fraction of cells in the microcapsules. In a complementary experimental study we compare the release rate constants of cells from shellac-cell microcapsules at different values of pH in the aqueous media. This study may allow fine-tuning of the rate of cell release in a variety of encapsulated cell products, including cell implants, probiotics, and live vaccines

Cell shape recognition by colloidal cell imprints : Energy of the cell-imprint interaction

The results presented in this study are aimed at the theoretical estimate of the interactions between a spherical microbial cell and the colloidal cell imprints in terms of the Derjaguin, Landau, Vervey, and Overbeek (DLVO) surface forces. We adapted the Derjaguin approximation to take into account the geometry factor in the colloidal interaction between a spherical target particle and a hemispherical shell at two different orientations with respect to each other. We took into account only classical DLVO surface forces, i.e., the van der Waals and the electric double layer forces, in the interaction of a spherical target cell and a hemispherical shell as a function of their size ratio, mutual orientation, distance between their surfaces, their respective surface potentials, and the ionic strength of the aqueous solution. We found that the calculated interaction energies are several orders higher when match and recognition between the target cell and the target cell imprint is achieved. Our analysis revealed that the recognition effect of the hemispherical shell towards the target microsphere comes from the greatly increased surface contact area when a full match of their size and shape is produced. When the interaction between the surfaces of the hemishell and the target cell is attractive, the recognition greatly amplifies the attraction and this increases the likelihood of them to bind strongly. However, if the surface interaction between the cell and the imprint is repulsive, the shape and size match makes this interaction even more repulsive and thus decreases the likelihood of binding. These results show that the surface chemistry of the target cells and their colloidal imprints is very important in controlling the outcome of the interaction, while the shape recognition only amplifies the interaction. In the case of nonmonotonous surface-to-surface interaction we discovered some interesting interplay between the effects of shape match and surface chemistry which is discussed in the paper. The results from this study establish the theoretical basis of cell shape recognition by colloidal cell imprints which, combined with cell killing strategies, could lead to an alternative class of cell shape selective antimicrobials, antiviral, and potentially anticancer therapies.</p

Triggered cell release from shellac-cell composite microcapsules

We report the fabrication of novel shellac-cell composite microcapsules with programmed release of cells upon change of pH in a narrow range. The microcapsules were prepared from yeast cells as a model for probiotics combined with aqueous solution of ammonium shellac doped with a pH sensitive polyelectrolyte, like carboxymethyl cellulose or polyacrylic acid. The cell dispersions in aqueous ammonium shellac were spray-dried or spray co-precipitated to yield composite shellac-cell microcapsules in which the cells retained their viability even when treated with aqueous solutions of very low pH and subjected to mechanical stress. We demonstrate two types of triggered release of yeast cells from these microcapsules with pH trigger and cell growth trigger and evaluate the microcapsule disintegration rates. Depending on the type of the polyelectrolyte integrated in the shellac microcapsules they can be programmed to give very versatile responses ranging from slow cell release to explosive swelling and disintegration at higher pH or exposure to growth media. We show that the cells retain their viability following their release from the microcapsules into the aqueous solution. Such composite microcapsules could find applications in formulations for protection and delivery of probiotic and other cell cultures with programmed and triggered release of the encapsulated cells in cell implants, including stem cells and live vaccines

Role of surfactants on the approaching velocity of two small emulsion drops

Here we present the exact solution of two approaching spherical droplets problem, at small Reynolds and Peclet numbers, taking into account surface shear and dilatational viscosities, Gibbs elasticity, surface and bulk diffusivities due to the presence of surfactant in both disperse and continuous phases. For large interparticle distances, the drag force coefficient, f, increases only about 50% from fully mobile to tangentially immobile interfaces, while at small distances, f can differ several orders of magnitude. There is significant influence of the degree of surface coverage, 0, on hydrodynamic resistance beta for insoluble surfactant monolayers. When the surfactant is soluble only in the continuous phase the bulk diffusion suppresses the Marangoni effect only for very low values of 0, while in reverse situation, the bulk diffusion from the drop phase is more efficient and the hydrodynamic resistance is lower. Surfactants with low value of the critical micelle concentration (CMC) make the interfaces tangentially immobile, while large CMC surfactants cannot suppress interfacial mobility, which lowers the hydrodynamic resistance between drops. For micron-sized droplets the interfacial viscosities practically block the surface mobility and they approach each other as solid spheres with high values of the drag coefficient