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Abstract In vertebrates, many organs, such as the kidney and the mammary gland form ductal structures based on the folding of epithelial sheets. The development of these organs relies on coordinated sorting of different cell lineages in both time and space, through mechanisms that remain largely unclear. Tissues are composed of several cell types with distinct biomechanical properties, particularly at cell‐cell and cell‐substrate boundaries. One hypothesis is that adjacent epithelial layers work in a coordinated manner to shape the tissue. Using in vitro experiments on model epithelial cells, differential expression of atypical Protein Kinase C iota (aPKCi), a key junctional polarity protein, is shown to reinforce cell epithelialization and trigger sorting by tuning cell mechanical properties at the tissue level. In a broader perspective, it is shown that in a heterogeneous epithelial monolayer, in which cell sorting occurs, forces arising from epithelial cell growth under confinement by surrounding cells with different biomechanical properties are sufficient to promote collective cell extrusion and generate emerging 3D organization related to spheroids and buds. Overall, this research sheds light on the role of aPKCi and the biomechanical interplay between distinct epithelial cell lineages in shaping tissue organization, providing insights into the understanding of tissue and organ development.

Abstract Changes in tissue geometry during developmental processes are associated with collective migration of cells. Recent experimental and numerical results suggest that these changes could leverage on the coexistence of nematic and hexatic orientational order at different length scales. How this multiscale organization is affected by the material properties of the cells and their substrate is presently unknown. In this study, we address these questions in monolayers of Madin-Darby canine kidney cells having various cell densities and molecular repertoires. At small length scales, confluent monolayers are characterized by a prominent hexatic order, independent of the presence of E-cadherin, monolayer density, and underlying substrate stiffness. However, all three properties affect the meso-scale tissue organization. The length scale at which hexatic order transits to nematic order, the “hexanematic” crossover scale, strongly depends on cell-cell adhesions and correlates with monolayer density. Our study demonstrates how epithelial organization is affected by mechanical properties, and provides a robust description of tissue organization during developmental processes.

Collective cell migration plays an essential role in various biological processes, such as development or cancer proliferation. While cell-cell interactions are clearly key determinants of collective cell migration, the physical mechanisms that control the emergence of cell clustering and collective cell migration are still poorly understood. In particular, observations have shown that binary cell-cell collisions generally lead to antialignment of cell polarities and separation of pairs—a process called contact inhibition of locomotion (CIL), which is expected to disfavor the formation of large-scale cell clusters with coherent motion even though the latter is often observed in tissues. To solve this puzzle, we adopt a joint experimental and theoretical approach to determine the large-scale dynamics of cell assemblies from elementary pairwise cell-cell interaction rules. We quantify experimentally binary cell-cell interactions and show that they can be captured by a minimal equilibriumlike pairwise asymmetric aligning interaction potential that reproduces the CIL phenomenology. We identify its symmetry class, build the corresponding active hydrodynamic theory, and show on general grounds that such asymmetric aligning interaction destroys large-scale clustering and ordering, leading instead to a liquidlike microphase of cell clusters of finite size and short lived polarity or to a fully dispersed isotropic phase. Finally, this shows that CIL-like asymmetric interactions in cellular systems—or general active systems—control cluster sizes and polarity, and can prevent large-scale coarsening and long-range polarity, except in the singular regime of dense confluent systems.

Abstract The resonant single active bridge topology (R‐SAB) operated in the half‐cycle discontinuous current mode (HC‐DCM) is a very attractive solution due to its high efficiency, low complexity and fixed voltage transfer ratio (DCX). However, as expected for a series‐resonant converter (SRC), its DCX operation depends on the resonant tank circuit‐parameters, parasitic capacitive elements and output load. Specially, at light and no‐load operation, when the system is extremely underdamped, it may present a large output overvoltage due to resonance interactions. This is of prime importance for converters using medium voltage (MV) SiC‐MOSFETs, which feature significant output capacitances that can lead to voltage breakdown of the rectifier semiconductors. Therefore, the supposed fixed‐voltage transfer ratio is not entirely valid and deserves a proper understanding due its criticality. This paper reviews the subject, clarifying its root cause and its multifactorial dependencies. Moreover, it provides a simple solution based on a variable dead‐time with fixed magnetizing current experimentally verified with a 300kW/1.8kV R‐SAB prototype implemented with MV SiC‐devices.

Uropathogenic strains of Escherichia coli (UPEC) are a leading cause of urinary tract infections (UTIs) and invasion involves Rho GTPase members, notably Rac1, to drive actin cytoskeleton rearrangement leading to engulfment. Here, Petracchini et al. provide evidence of an ECM stiffnessmodulated role of Optineurin (OPTN), which regulates HACE1-dependant Rac1 activity and thus controls integrinmediated mechanotransduction and bacterial invasion.

In vertebrates, many organs, such as the kidney and the mammary gland form ductal structures based on the folding of epithelial sheets. The development of these organs relies on coordinated sorting of different cell lineages in both time and space, through mechanisms that remain largely unclear. Tissues are composed of several cell types with distinct biomechanical properties, particularly at cell‐cell and cell‐substrate boundaries. One hypothesis is that adjacent epithelial layers work in a coordinated manner to shape the tissue. Using in vitro experiments on model epithelial cells, differential expression of atypical Protein Kinase C iota (aPKCi), a key junctional polarity protein, is shown to reinforce cell epithelialization and trigger sorting by tuning cell mechanical properties at the tissue level. In a broader perspective, it is shown that in a heterogeneous epithelial monolayer, in which cell sorting occurs, forces arising from epithelial cell growth under confinement by surrounding cells with different biomechanical properties are sufficient to promote collective cell extrusion and generate emerging 3D organization related to spheroids and buds. Overall, this research sheds light on the role of aPKCi and the biomechanical interplay between distinct epithelial cell lineages in shaping tissue organization, providing insights into the understanding of tissue and organ development. [ABSTRACT FROM AUTHOR]

Biological tissues are composed of various cell types working cooperatively to perform their respective function within organs and the whole body. During development, embryogenesis followed by histogenesis relies on orchestrated division, death, differentiation and collective movements of cellular constituents. These cells are anchored to each other and/or the underlying substrate through adhesion complexes and they regulate force generation by active cytoskeleton remodeling. The resulting changes in contractility at the level of each single cell impact tissue architecture and remodeling by triggering changes in cell shape, cell movement and remodeling of the surrounding environment. These out of equilibrium processes occur through cellular energy consumption, allowing biological systems to be described by active matter physics. Cytoskeleton filaments, bacterial and eukaryotic cells can be considered as a sub-class of active matter termed “active nematics”. These biological objects can be modelled as rod-like elements to which nematic liquid crystal theories can be applied. In this work, using an analogy from liquid crystal physics, we show that cell sorting and boundary formation can be explained using differences in nematic activity. This difference in nematic activity arises from a balance of inter- and intra-cellular activity.

Abstract Grid connection of remote offshore wind‐parks uses high‐voltage direct current technology and in order to reduce costs and losses and maximise profitability, semiconductor power losses must be minimised. To properly choose the semiconductors, it is necessary to estimate their losses for a large number of operating conditions. This article deals with a modelling approach to calculate power losses for many such operating conditions, based on measured semiconductor characteristics and the chosen multilevel modulation strategy. The case of the integrated gate‐commutated thyristor is considered because, for a given device rating, it is possible to select an integrated gate‐commutated thyristor benefiting from the best trade‐off between on‐state losses and turn‐off losses, thus minimising the power losses of the two end‐stations.

Cells can modify their environment by depositing biochemical signals or mechanically remodelling the extracellular matrix; the impact of such self-induced environmental perturbations on cell trajectories at various scales remains unexplored. Here authors show that motile cells leave long-lived physicochemical footprints along their way, which determine their future path.

The global development of high-voltage direct-current (HVDC) systems in fields such as renewable energy sources, interconnection of asynchronous grids or power transmission over great distances, is unquestionably important. Though widely used, the modular multilevel converter with half-bridge cells is sensitive to DC pole-to-pole faults and the time-response of the protections is critical. Reliability and availability are paramount: circuit-breakers must minimize the effects of any fault on the converter, while ensuring rapid restart. This paper focuses on the modelling aspects to analyse the behaviour of HVDC stations during DC pole-to-pole faults, using either AC or DC circuit-breakers, with different parameters. The proposed model can represent the main issues met by the converter cells during DC faults, such as semiconductor overcurrents and overvoltages, allowing a proper design of the cells.

The organization and force-generating property of actomyosin dictate the plasticity and behaviour of cells but the spatio-temporal regulation of this network is unclear. Here, the authors show that coupling between EpCAM/RhoA co-trafficking and actomyosin rearrangement is pivotal during cell spreading and polarization.

This paper presents an averaged real-time model of an arbitrary size MVDC railway system. In contrast to references already available in the literature, focusing mainly on specific parts of such a railway network (e.g. power converter installed in a locomotive), this paper offers a thorough insight into the modeling of every part belonging to it. Through a set of reasonable assumptions, the concept of a sector is presented allowing for a straightforward synthesis of any MVDC railway network. Thereafter, real-time models of catenaries, rails, trains, as well as power converters supplying the system are presented in a comprehensive manner. Without loss of generality, the system analyzed hereafter represents a 200 km section of a double-track EuroCity line powered by an actively fed electrification system with three transformer-rectifier groups and two modular multilevel converters. The proposed modeling approach was verified on a large-scale hardware-in-the-loop system comprising one RT Box 3, hosting the model of the exemplary railway network, and two modular multilevel converter digital twins relying on the use of industrial ABB PEC800 controllers.

Cell extrusion regulates monolayer cell density and is critical in maintaining epithelia integrity, which has implications in homeostasis, development, and cancer progression. Here the authors describe how monolayer integrate mechanical signals from tissue mechanics, cell-cell adhesion, cell-substrate adhesion and cytoskeleton coordinate cell extrusion.

Abstract Background Cancer cells cooperate with cells that compose their environment to promote tumor growth and invasion. Among them, adipocytes provide lipids used as a source of energy by cancer cells and adipokines that contribute to tumor expansion. Mechanisms supporting the dynamic interactions between cancer cells and stromal adipocytes, however, remain unclear. Methods We set-up a co-culture model with breast cancer cells grown in 3D as mammospheres and human adipocytes to accurately recapitulate intrinsic features of tumors, such as hypoxia and cancer cell–adipocytes interactions. Results Herein, we observed that the lipid droplets’ size was reduced in adipocytes adjacent to the mammospheres, mimicking adipocyte morphology on histological sections. We showed that the uncoupling protein UCP1 was expressed in adipocytes close to tumor cells on breast cancer histological sections as well as in adipocytes in contact with the mammospheres. Mammospheres produced adrenomedullin (ADM), a multifactorial hypoxia-inducible peptide while ADM receptors were detected in adipocytes. Stimulation of adipocytes with ADM promoted UCP1 expression and increased HSL phosphorylation, which activated lipolysis. Invalidation of ADM in breast cancer cells dramatically reduced UCP1 expression in adipocytes. Conclusions Breast tumor cells secreted ADM that modified cancer–associated adipocytes through paracrine signaling, leading to metabolic changes and delipidation. Hence, ADM appears to be crucial in controlling the interactions between cancer cells and adipocytes and represents an excellent target to hinder them.