How cells align to structured collagen fibrils: a hybrid cellular Potts and molecular dynamics model with dynamic mechanosensitive focal adhesions.

Many mammalian cells, including endothelial cells and fibroblasts, align and elongate along the orientation of extracellular matrix (ECM) fibers in a gel when cultured . During cell elongation, clusters of focal adhesions (FAs) form near the poles of the elongating cells. FAs are mechanosensitive clusters of adhesions that grow under mechanical tension exerted by the cells' pulling on the ECM and shrink when the tension is released.

2'-Fucosyllactose helps butyrate producers outgrow competitors in infant gut microbiota simulations.

A reduced capacity for butyrate production by the early infant gut microbiota is associated with negative health effects, such as inflammation and the development of allergies. Here, we develop new hypotheses on the effect of the prebiotic galacto-oligosaccharides (GOS) or 2'-fucosyllactose (2'-FL) on butyrate production by the infant gut microbiota using a multiscale, spatiotemporal mathematical model of the infant gut. The model simulates a community of cross-feeding gut bacteria in metabolic detail.

The shapes of elongating gastruloids are consistent with convergent extension driven by a combination of active cell crawling and differential adhesion.

Gastruloids have emerged as highly useful in vitro models of mammalian gastrulation. One of the most striking features of 3D gastruloids is their elongation, which mimics the extension of the embryonic anterior-posterior axis. Although axis extension is crucial for development, the underlying mechanism has not been fully elucidated in mammalian species.

A life-history allele of large effect shortens developmental time in a wild insect population.

Developmental time is a key life-history trait with large effects on Darwinian fitness. In many insects, developmental time is currently under strong selection to minimize ecological mismatches in seasonal timing induced by climate change. The genetic basis of responses to such selection, however, is poorly understood.

Deformability and collision-induced reorientation enhance cell topotaxis in dense microenvironments.

In vivo, cells navigate through complex environments filled with obstacles such as other cells and the extracellular matrix. Recently, the term "topotaxis" has been introduced for navigation along topographic cues such as obstacle density gradients. Experimental and mathematical efforts have analyzed topotaxis of single cells in pillared grids with pillar density gradients.

Hybrid cellular Potts and bead-spring modeling of cells in fibrous extracellular matrix.

The mechanical interaction between cells and the extracellular matrix (ECM) is fundamental to coordinate collective cell behavior in tissues. Relating individual cell-level mechanics to tissue-scale collective behavior is a challenge that cell-based models such as the cellular Potts model (CPM) are well-positioned to address. These models generally represent the ECM with mean-field approaches, which assume substrate homogeneity.

Computational modeling of cambium activity provides a regulatory framework for simulating radial plant growth.

Precise organization of growing structures is a fundamental process in developmental biology. In plants, radial growth is mediated by the cambium, a stem cell niche continuously producing wood (xylem) and bast (phloem) in a strictly bidirectional manner. While this process contributes large parts to terrestrial biomass, cambium dynamics eludes direct experimental access due to obstacles in live-cell imaging.

Evolution of genome fragility enables microbial division of labor.

Division of labor can evolve when social groups benefit from the functional specialization of its members. Recently, a novel means of coordinating the division of labor was found in the antibiotic-producing bacterium Streptomyces coelicolor, where specialized cells are generated through large-scale genomic re-organization. We investigate how the evolution of a genome architecture enables such mutation-driven division of labor, using a multiscale computational model of bacterial evolution.

A new model of Notch signalling: Control of Notch receptor cis-inhibition via Notch ligand dimers.

All tissue development and replenishment relies upon the breaking of symmetries leading to the morphological and operational differentiation of progenitor cells into more specialized cells. One of the main engines driving this process is the Notch signal transduction pathway, a ubiquitous signalling system found in the vast majority of metazoan cell types characterized to date. Broadly speaking, Notch receptor activity is governed by a balance between two processes: 1) intercellular Notch transactivation triggered via interactions between receptors and ligands expressed in neighbouring cells; 2) intracellular cis inhibition caused by ligands binding to receptors within the same cell.

Scaling relations for auxin waves.

We analyze an 'up-the-gradient' model for the formation of transport channels of the phytohormone auxin, through auxin-mediated polarization of the PIN1 auxin transporter. We show that this model admits a family of travelling wave solutions that is parameterized by the height of the auxin-pulse. We uncover scaling relations for the speed and width of these waves and verify these rigorous results with numerical computations.

A Multiscale Spatiotemporal Model Including a Switch from Aerobic to Anaerobic Metabolism Reproduces Succession in the Early Infant Gut Microbiota.

The human intestinal microbiota starts to form immediately after birth and is important for the health of the host. During the first days, facultatively anaerobic bacterial species generally dominate, such as . These are succeeded by strictly anaerobic species, particularly species.

Implementing Computational Modeling in Tissue Engineering: Where Disciplines Meet.

In recent years, the mathematical and computational sciences have developed novel methodologies and insights that can aid in designing advanced bioreactors, microfluidic setups or organ-on-chip devices, in optimizing culture conditions, or predicting long-term behavior of engineered tissues . In this review, we introduce the concept of computational models and how they can be integrated in an interdisciplinary workflow for Tissue Engineering and Regenerative Medicine (TERM). We specifically aim this review of general concepts and examples at experimental scientists with little or no computational modeling experience.

Computational modelling of cell motility modes emerging from cell-matrix adhesion dynamics.

Lymphocytes have been described to perform different motility patterns such as Brownian random walks, persistent random walks, and Lévy walks. Depending on the conditions, such as confinement or the distribution of target cells, either Brownian or Lévy walks lead to more efficient interaction with the targets. The diversity of these motility patterns may be explained by an adaptive response to the surrounding extracellular matrix (ECM).

Modeling Plant Tissue Development Using VirtualLeaf.

Cell-based computational modeling and simulation are becoming invaluable tools in analyzing plant development. In a cell-based simulation model, the inputs are behaviors and dynamics of individual cells and the rules describing responses to signals from adjacent cells. The outputs are the growing tissues, shapes, and cell-differentiation patterns that emerge from the local, chemical, and biomechanical cell-cell interactions.

Twisting of the zebrafish heart tube during cardiac looping is a -dependent and tissue-intrinsic process.

Organ laterality refers to the left-right asymmetry in disposition and conformation of internal organs and is established during embryogenesis. The heart is the first organ to display visible left-right asymmetries through its left-sided positioning and rightward looping. Here, we present a new zebrafish loss-of-function allele for , which displays defective rightward cardiac looping morphogenesis.

A Novel Function of TLR2 and MyD88 in the Regulation of Leukocyte Cell Migration Behavior During Wounding in Zebrafish Larvae.

Toll-like receptor (TLR) signaling via myeloid differentiation factor 88 protein (MyD88) has been indicated to be involved in the response to wounding. It remains unknown whether the putative role of MyD88 in wounding responses is due to a control of leukocyte cell migration. The aim of this study was to explore whether TLR2 and MyD88 are involved in modulating neutrophil and macrophage cell migration behavior upon zebrafish larval tail wounding.

Evolution of multicellularity by collective integration of spatial information.

At the origin of multicellularity, cells may have evolved aggregation in response to predation, for functional specialisation or to allow large-scale integration of environmental cues. These group-level properties emerged from the interactions between cells in a group, and determined the selection pressures experienced by these cells. We investigate the evolution of multicellularity with an evolutionary model where cells search for resources by chemotaxis in a shallow, noisy gradient.

Cell Shape and Durotaxis Explained from Cell-Extracellular Matrix Forces and Focal Adhesion Dynamics.

Many cells are small and rounded on soft extracellular matrices (ECM), elongated on stiffer ECMs, and flattened on hard ECMs. Cells also migrate up stiffness gradients (durotaxis). Using a hybrid cellular Potts and finite-element model extended with ODE-based models of focal adhesion (FA) turnover, we show that the full range of cell shape and durotaxis can be explained in unison from dynamics of FAs, in contrast to previous mathematical models.

Autocrine inhibition of cell motility can drive epithelial branching morphogenesis in the absence of growth.

Epithelial branching morphogenesis drives the development of organs such as the lung, salivary gland, kidney and the mammary gland. It involves cell proliferation, cell differentiation and cell migration. An elaborate network of chemical and mechanical signals between the epithelium and the surrounding mesenchymal tissues regulates the formation and growth of branching organs.

Mechanical interplay between cell shape and actin cytoskeleton organization.

We investigate the mechanical interplay between the spatial organization of the actin cytoskeleton and the shape of animal cells adhering on micropillar arrays. Using a combination of analytical work, computer simulations and in vitro experiments, we demonstrate that the orientation of the stress fibers strongly influences the geometry of the cell edge. In the presence of a uniformly aligned cytoskeleton, the cell edge can be well approximated by elliptical arcs, whose eccentricity reflects the degree of anisotropy of the cell's internal stresses.

Topotaxis of active Brownian particles.

Recent experimental studies have demonstrated that cellular motion can be directed by topographical gradients, such as those resulting from spatial variations in the features of a micropatterned substrate. This phenomenon, known as topotaxis, has been extensively studied for topographical gradients at the subcellular scale, but can also occur in the presence of a spatially varying density of cell-sized features. Such a large-scale topotaxis has recently been observed in highly motile cells that persistently crawl within an array of obstacles with smoothly varying lattice spacing.

Somite Division and New Boundary Formation by Mechanical Strain.

Somitogenesis, the primary segmentation of the vertebrate embryo, is associated with oscillating genes that interact with a wave of cell differentiation. The necessity of cell-matrix adherence and embryonic tension, however, suggests that mechanical cues are also involved. To explicitly investigate this, we applied surplus axial strain to live chick embryos.

Chiral stresses in nematic cell monolayers.

Recent experiments on monolayers of spindle-like cells plated on adhesive stripe-shaped domains have provided a convincing demonstration that certain types of collective phenomena in epithelia are well described by active nematic hydrodynamics. While recovering some of the hallmark predictions of this framework, however, these experiments have also revealed a number of unexpected features that could be ascribed to the existence of chirality over length scales larger than the typical size of a cell. In this article we elaborate on the microscopic origin of chiral stresses in nematic cell monolayers and investigate how chirality affects the motion of topological defects, as well as the collective motion in stripe-shaped domains.