Biology subjects

Merks, R. M. H.

Publications and source records attributed to Merks, R. M. H..

At least 19 recordsLinked to original sources

bioRxiv2026

Laminin and Fibronectin Cooperate to Guide Endothelial Self-Organization During Intersegmental Vessel Formation

Endothelial sprouts must integrate cell-intrinsic self-organization with external guidance cues to build stereotyped vascular patterns. During zebrafish intersegmental vessel (ISV) formation, the extra-cellular matrix in the intersomitic space is enriched in laminin and fibronectin, but how these cues guide sprouting remains unclear. We integrated live imaging, perturbation experiments, rescue assays, and mathematical modeling to test whether these matrix components canalize endothelial behavior. Partial loss of laminin or fibronectin slowed endothelial sprouting without abolishing overall ISV formation. In a hybrid mathematical model coupling endothelial self-organization to a deformable extracellular matrix, reduced matrix density predicted slower sprouting and increased vessel fusion. Consistent with this prediction, combined laminin and fibronectin knockdown produced severe ISV mispatterning, including ectopic fusion events and network-like vascular arrangements. Chimeric fibronectin mRNAs rescued vascular patterning and associated somite defects. Comparison of lama1/lama4/fn1a and lama1/lama4/fn1b morphants suggested that somite disorganization exacerbates ISV defects, but is not required for them. Together, our results support a guided self-organization model in which laminin and fibronectin cooperate with other tissue cues to confine endothelial self-organization to the intersomitic space and ensure robust angiogenic patterning.

developmental biology↗

bioRxiv2024

Falsifying computational models of angiogenesis through quantitative comparison with in vitro models

During angiogenesis, endothelial cells expand the vasculature by migrating from existing blood vessels, proliferating and collectively organizing into new capillaries. In vitro and in vivo experimentation is instrumental for identifying the molecular players and cell behaviour that regulate angiogenesis. Alongside experimental work, computational and mathematical models of endothelial cell network formation have helped to analyse if the current molecular and cellular understanding of endothelial cell behaviour is sufficient to explain the formation of endothelial cell networks. As input, the models take (a subset of) the current knowledge or hypotheses of single cell behaviour and capture it into a dynamical, mathematical description. As output, they predict the multicellular behaviour following from the actions of many individual cells, i.e., formation of a vascular-like network. Paradoxically, computational modelling based on different assumptions, i.e., completely different, sometimes non-intersecting sets of observed single cell behaviour, can reproduce the same angiogenesis-like multicellular behaviour, making it practically impossible to decide which, if any, of these models is correct. Here we present dynamical analyses of time-lapses of in vitro endothelial cell network formation experiments and compare these with dynamic analyses of three mathematical models: (1) the cell elongation model; (2) the contact-inhibited chemotaxis model; and (3) the mechanical cell-cell communication model. We extract a variety of dynamical characteristics of endothelial cell network formation using a custom time-lapse video analysis pipeline in ImageJ. We compare the dynamical network characteristics of the in vitro experiments to those of the cellular networks produced by the computational models. We test the response of the in silico dynamical cell network characteristics to changes in cell density and make related changes in the in vitro experiments. Of the three computational models that we have considered, the cell elongation model best captures the remodelling phase of in vitro endothelial cell network formation. Furthermore, in the in vitro model, the final size and number of lacunae in the network are independent of the initial cell density. This observation is also reproduced in the cell elongation model, but not in the other two models that we have considered. Altogether, we present an approach to model validation based on comparisons of time-resolved data and variations of model conditions. Author SummaryUnderstanding how blood vessels grow and organise into well-structured networks is crucial for many clinical applications, from wound healing to cancer treatment. The growth of blood vessels, known as angiogenesis, involves endothelial cells migrating, proliferating, and forming new vascular structures. Angiogenesis is studied through biological experiments, but mathematical models are also used to test whether our understanding of cell behaviour is sufficient to explain cell network formation. Models assuming chemotaxis, elongated cell shape, contact inhibition or mechanical cell-cell communication often produce similar results despite the large differences in the underlying assumptions, making it difficult to determine which model is most accurate. In this study, we analysed time-lapse videos of endothelial cell network formation and compared these with three computational models: (1) the cell elongation model, (2) the contact-inhibited chemotaxis model, and (3) the mechanical cell-cell communication model. By examining the dynamics of network formation and testing how they change with cell density, we found that the cell elongation model best captures key aspects of the real-life cell network remodelling process. This approach highlights the importance of time-resolved data in evaluating computational models and provides a framework for refining our understanding of angiogenesis.

developmental biology↗

bioRxiv2024

Enhanced Cell Wall Mechanics in VirtualLeaf Enable Realistic Simulations of Plant Tissue Dynamics

Computational modelling has become essential to advancing our understanding of plant developmental and physiological processes, necessitating the development of new computational approaches and software. Here, we present VirtualLeaf-2.0, an updated version of this modelling framework for the biophysical and biomechanical interactions between cells in plant tissues, with novel features for more detailed modelling of the cell wall. In particular, the updated version of VirtualLeaf enables detailed modelling of variations in cell wall stability and cell wall sliding up to the level of individual cell wall elements. The plant cell wall plays a pivotal role in plant development and survival, with younger cells generally having thinner, more flexible (primary) walls than older cells. Cell wall stability is further affected by signalling in growth processes and pathogen infection. The improvements of VirtualLeaf lay the groundwork for using VirtualLeaf to address novel questions involving plant tissue dynamics during growth, tissue formation and pathogen defence, as illustrated with example simulations.

bioinformatics↗

bioRxiv2024

Simulations of the infant gut microbiota suggest that complex ecological interactions regulate effects of human milk oligosaccharides on microbial mucin consumption

Intestinal mucin acts as a barrier protecting the infant gut wall against diseases such as colitis and rotavirus. In vitro experiments have shown that the gut microbiota of breastfed infants consumes less mucin than the microbiota of non-breastfed infants, but the mechanisms are incompletely understood. The main difference between human milk and most infant formulas is the presence of human milk oligosaccharides (HMOs) in human milk. We hypothesize that HMOs protect mucin by stimulating non-mucin consuming bacteria. To understand the un-derlying mechanisms we developed a computational model that describes the metabolism and ecology of the infant gut microbiota. Model simulations suggest that extracellular digestion of the HMO 2-fucosyllactose by the mucin-consumer Bifidobacterium bifidum may make this species vulnerable to competitors. The digestion products of HMOs become public goods that can be consumed by competing species such as Bacteroides vulgatus instead.Bifidobacterium longum, which does not consume mucin or produce public goods, can then become dominant, despite growing less efficiently on HMOs in monocultures than B. bifidum. In conclusion, our model simulations suggest that, through complex ecological interactions, HMOs may help lower mucin consumption by stimulating the non-mucin consumer B. longum at the expense of the mucin consumer B. bifidum.

systems biology↗

bioRxiv2024

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, tend to align and elongate with the orientation of extracellular matrix (ECM) fibers in a gel when cultured in vitro. 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 due to the cells pulling on the ECM, and shrink when the tension is released. Using a mathematical modeling approach, we study the hypothesis that reciprocity between cells and the ECM drives cell shape changes. We show that FAs are preferentially stabilized along the orientation of ECM fibers, where the cells can generate more tension than perpendicular to the ECM fibers. We present a hybrid cellular Potts model that represents the ECM as an off-the-lattice network of cross-linked deformable fibers, whereas the cell is represented on the lattice. Multiple FAs are modeled individually by an independent rate of FA assembly and a mechanoresponsive FA disassembly. The resulting computational model predicts stiffness-dependent cell spreading and local ECM remodelling, and ECM-alignment dependent cell elongation. The effects combined suffice to explain how cell morphology is determined by local ECM structure and mechanics.

biophysics↗

bioRxiv2024

In silico model suggests that interdigitation promotes robust activation of atrial cells by pacemaker cells

The heartbeat is initiated by electrical pulses generated by a specialized patch of cells called the sinoatrial node (SAN), located on top of the right upper chamber, and then passed on to the atrium. Cardiac arrhythmias may arise if these electrical pulses fail to propagate toward the atrial cells. This computational modeling study asks how the morphology of the interface between sinoatrial (pacemaker) cells and atrial cells can influence the robustness of pulse propagation. Due to its strong negative potential, the atrium may suppress the pacemaker activity of the SAN if the electrical coupling between atrial cells is too strong. If the electrical coupling is too weak, however, the pacemaker cells cannot activate the atrial cells due to a source-sink mismatch. The SAN and atrium are connected through interdigitating structures, which are believed to contribute to the robustness of action potentials and potentially solve this trade-off. Here we investigate this interdigitation hypothesis using a hybrid model, integrating the cellular Potts model (CPM) for cellular morphology and partial-differential equations-based electrophysiological models for pulse propagation. Systematic examination of interdigitation patterns revealed that a symmetric geometry with medium-sized protrusions can prevent exit blocks. We conclude that interdigitation of SAN cells and atrial cells can promote robust propagation of action potentials toward the atrial tissue but only if the protrusions are of sufficient size and synchronicity of the action potential wave is maintained due to symmetry. This study not only highlights essential design principles for in vitro models of cardiac arrhythmias, but also provides insights into the occurrence of exit blocks in vivo. Author summaryOur hearts beat automatically and robustly. This autonomous heartbeat is initiated by electrical pulses generated by a specialized patch of cells called the sinoatrial node, located on top of the right upper chamber. These pulses can be interpreted as electrical signals that allow the heart muscle to contract. The heart muscle cells surrounding the sinoatrial node tend to hinder this spontaneous activation because of a mismatch in electrical properties. Therefore, the pacemaker cells must be sufficiently electrically insulated from their surroundings. However, full insulation of the pacemaker cells would hinder propagation of the activation pulse toward the rest of the heart. A common hypothesis is that the sinoatrial node is fully insulated, except for some specialized pathways. We have studied the arrangement of different cell types within these pathways with the central question: how should the sinoatrial node and atrium be connected to ensure robust propagation of the electrical pulse? We implemented a computational model inspired by in vitro experimental setups and found several relevant mechanisms. For example, we found that a folding-finger-like structure between the cell types can dramatically improve the robustness of action potentials propagating in such a tissue, provided that the folds do not become too small. This study may help improve design of in vitro models of sinoatrial node diseases.

systems biology↗

bioRxiv2024

Factors that influence the caste ratio in a bacterial division of labour

Colonies of the bacteria Streptomyces coelicolor divide labour between cells that specialize on growth and sporulation and cells that specialize on antibiotic production. This division of labour arises due to costly chromosome deletions in the antibiotic overproducers. However, little is known about when and where these mutations occur or whether their frequency - which we liken to the caste ratio in social insects - is phenotypically plastic. To elucidate changes in the proportions of specialized cells (measured as the mutation frequency), we sampled S. coelicolor colonies grown under different conditions. Temporally, mutation frequency increased linearly with colony age and size. Spatially, mutations accumulated disproportionately in the colony center, despite greater growth and sporulation at the periphery. Exposing colonies to sub-inhibitory concentrations of some antibiotics, a competitive cue in Streptomyces, increased mutation frequencies. Finally, direct competition with other Streptomyces that naturally produce antibiotics increased mutation frequencies, while also increasing spore production. Our findings provide insights into the intrinsic and environmental factors driving division of labor in Streptomyces colonies by showing that mutation frequencies are dynamic and responsive to the competitive environment. These results show that chromosome deletions are phenotypically plastic and suggest that Streptomyces can flexibly adjust their caste ratio.

evolutionary biology↗

bioRxiv2023

A combination of convergent extension and differential adhesion explains the shapes of elongating gastruloids

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. Gastruloids provide an opportunity to study this morphogenic process in vitro. Here, we measure and quantify the shapes of elongating gastruloids and show, by Cellular Potts model simulations, that a combination of convergent extension and differential adhesion can explain the observed shapes. We reveal that differential adhesion alone is insufficient and also directly observe hallmarks of convergent extension by time-lapse imaging of gastruloids. Finally, we show that gastruloid elongation can be abrogated by inhibition of the Rho kinase pathway, which is involved in convergent extension in vivo. All in all, our study demonstrates, how gastruloids can be used to elucidate morphogenic processes in embryonic development.

developmental biology↗

bioRxiv2023

2'-Fucosyllactose helps butyrate producers outgrow competitors in the infant gut

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 at metabolic detail. It represents the gut microbiome as a grid of bacterial populations that exchange intermediary metabolites, using 20 different subspecies-specific metabolic networks taken from the AGORA database. The simulations predict that both GOS and 2-FL promote the growth of Bifidobacterium, whereas butyrate producing bacteria are only consistently abundant in the presence of propane-1,2-diol, a product of 2-FL metabolism. The results suggest that in absence of prebiotics or in presence of only GOS, bacterial species, including Cutibacterium acnes and Bacteroides vulgatus, outcompete butyrate producers by feeding on intermediary metabolites. In presence of 2-FL, however, production of propane-1,2-diol specifically supports butyrate producers.

systems biology↗

bioRxiv2022

Modelling the mechanical cross-talk between cells and fibrous extracellular matrices using hybrid cellular Potts and molecular dynamics methods

The mechanical interaction between cells and the extracellular matrix (ECM) is fundamental to coordinate collective cell behavior in multicellular tissues. Relating individual cell-level mechanics to tissue-scale collective behavior is an outstanding challenge which 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. This assumption breaks down with fibrous ECM, which has non-trivial structure and mechanics. Here, we extend the CPM with a bead-spring chain model of ECM fiber networks modelled using molecular dynamics. We model contractile cells pulling with discrete focal adhesion-like sites on the ECM fiber network, and demonstrate agreement with experimental spatiotemporal fiber densification and displacement. We show that contractile cell forces propagate over multiple cell radii scaling with power law exponent of {approx} -0.5 typical of viscoelastic ECM. Further, we use in silico atomic force microscopy to measure local cell-induced network stiffening consistent with experiments. Our model lays the foundation to investigate how local and long-ranged cell-ECM mechanobiology contributes to multicellular morphogenesis.

biophysics↗

bioRxiv2022

Stress fibers orient traction forces on micropatterns: A hybrid cellular Potts model study

Adhering cells exert traction forces on the underlying substrate. We numerically investigate the intimate relation between traction forces, the structure of the actin cytoskeleton, and the shape of cells adhering to adhesive micropatterned substrates. By combining the Cellular Potts Model with a model of cytoskeletal contractility, we reproduce prominent anisotropic features in previously published experimental data on fibroblasts, endothelial cells, and epithelial cells on adhesive micropatterned substrates. Our work highlights the role of cytoskeletal anisotropy in the generation of cellular traction forces, and provides a computational strategy for investigating stress fiber anisotropy in dynamical and multicellular settings. Author summaryCells that make up multicellular life perform a variety of mechanical tasks such as pulling on surrounding tissue to close a wound. The mechanisms by which cells perform these tasks are, however, incompletely understood. In order to better understand how they generate forces on their environment, cells are often studied in vitro on compliant substrates, which deform under the so called "traction forces" exerted by the cells. Mathematical models complement these experimental approaches because they help to interpret the experimental data, but most models for traction forces on adhesive substrates assume that cells contract isotropically, i.e., they do not contract in a specific direction. However, many cell types contain organized structures of stress fibers - strong contracting cables inside the cell - that enable cells to exert forces on their environment in specific directions only. Here we present a computational model that predicts both the orientations of these stress fibers as well as the forces that cells exert on the substrates. Our model reproduces both the orientations and magnitudes of previously reported experimental traction forces, and could serve as a starting point for exploring mechanical interactions in multicellular settings.

biophysics↗

bioRxiv2021

A multiscale spatiotemporal model explains succession in the early infant gut microbiota as a switch from aerobic to anaerobic metabolism

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 Enterobacteriaceae. These are succeeded by strictly anaerobic species, particularly Bifidobacterium species. An early transition to Bifidobacterium species is associated with health benefits: for example, Bifidobacterium species repress growth of pathogenic competitors and modulate the immune response. Succession to Bifidobacterium is thought to be due to consumption of intracolonic oxygen present in newborns by facultative anaerobes, including Enterobacteriaceae. To study if oxygen depletion suffices for the transition to Bifidobacterium species, here we introduce a multiscale mathematical model that considers metabolism, spatial bacterial population dynamics and cross-feeding. Using publicly available metabolic network data from the AGORA collection, the model simulates ab initio the competition of strictly and facultatively anaerobic species in a gut-like environment under the influence of lactose and oxygen. The model predicts that individual differences in intracolonic oxygen in newborn infants can explain the observed individual variation in succession to anaerobic species, in particular Bifidobacterium species. Bifidobacterium species become dominant in the model by using the bifid shunt, which allows Bifidobacterium to switch to sub-optimal yield metabolism with fast growth at high lactose concentrations as predicted here using flux-balance analysis. The computational model thus allows us to test the internal plausibility of hypotheses for bacterial colonization and succession in the infant colon. IMPORTANCEThe composition of the infant microbiota has a great impact on infant health, but its controlling factors are still incompletely understood. The frequently dominant anaerobic Bifidobacterium species benefit health, e.g., because they can keep harmful competitors under control and modulate the intestinal immune response. Controlling factors could include nutritional composition and intestinal mucus composition, as well as environmental factors, such as antibiotics. We introduce a modeling framework of a metabolically realistic intestinal microbial ecology in which hypothetical scenarios can be tested and compared. We present simulations that suggest that greater levels of intra-intestinal oxygenation more strongly delay the dominance of Bifidobacterium species, explaining the observed variety of microbial composition and demonstrating the use of the model for hypothesis generation. The framework allows us to test a variety of controlling factors, including intestinal mixing and transit time. Future versions will also include detailed modeling of oligosaccharide and mucin metabolism.

systems biology↗

bioRxiv2021

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 Levy walks. Depending on the conditions, such as confinement or the distribution of target cells, either Brownian or Levy 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). Indeed, depending on the ECM composition, lymphocytes either display a floating motion without attaching to the ECM, or sliding and stepping motion with respectively continuous or discontinuous attachment to the ECM, or pivoting behaviour with sustained attachment to the ECM. Moreover, on the long term, lymphocytes either perform a persistent random walk or a Brownian-like movement depending on the ECM composition. How the ECM affects cell motility is still incompletely understood. Here, we integrate essential mechanistic details of the lymphocyte-matrix adhesions and lymphocyte intrinsic cytoskeletal induced cell propulsion into a Cellular Potts model (CPM). We show that the combination of de novo cell-matrix adhesion formation, adhesion growth and shrinkage, adhesion rupture, and feedback of adhesions onto cell propulsion recapitulates multiple lymphocyte behaviours, for different lymphocyte subsets and various substrates. With an increasing attachment area and increased adhesion strength, the cells speed and persistence decreases. Additionally, the model can predict short-term persistent with long-term subdiffusive motility, showing a pivoting motion. For small adhesion areas, we observe that the spatial distribution of adhesions influences cell motility. Small adhesions at the front allow for more persistent motion than larger clusters at the back, despite a similar total adhesion area. In conclusion, we present an integrated framework to simulate the effects of ECM proteins on cell-matrix adhesion dynamics. The model reveals a sufficient set of principles explaining the plasticity of lymphocyte motility. Author summaryDuring immunosurveillance, lymphocytes patrol through tissues to interact with cancer cells, other immune cells, and pathogens. The efficiency of this process depends on the kinds of trajectories taken, ranging from simple Brownian walks to Levy walks. The composition of the extracellular matrix (ECM), a network of macromolecules, affects the formation of cell-matrix adhesions, thus strongly influencing the way lymphocytes move. Here, we present a model of lymphocyte motility driven by adhesions that grow, shrink and rupture in response to the ECM and cellular forces. Compared to other models, our model is computationally light making it suitable for generating long term cell track data, while still capturing actin dynamics and adhesion turnover. Our model suggests that cell motility is affected by the force required to break adhesions and the rate at which new adhesions form. Adhesions can promote cell protrusion by inhibiting retrograde actin flow. After introducing this effect into the model, we found that it reduces the cellular diffusivity and that it promotes stick-slip behaviour. Furthermore, location and size of adhesion clusters determined cell persistence. Overall, our model explains the plasticity of lymphocyte behaviour in response to the ECM.

cell biology↗

bioRxiv2021

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 division of labor was found in the antibiotic-producing bacterium Streptomyces coelicolor, where functionally specialized cells are generated through large-scale genomic re-organization. Here, we investigate how the evolution of a genome architecture enables such mutation-driven division of labor, using a multi-scale mathematical model of bacterial evolution. We let bacteria compete on the basis of their antibiotic production and growth rate in a spatially structured environment. Bacterial behavior is determined by the structure and composition of their genome, which encodes antibiotics, growth-promoting genes and fragile genomic loci that can induce chromosomal deletions. We find that a genomic organization evolves that partitions growth-promoting genes and antibiotic-coding genes to distinct parts of the genome, separated by fragile genomic loci. Mutations caused by these fragile sites mostly delete growth-promoting genes, generating antibiotic-producing mutants from non-producing (and weakly-producing) progenitors, in agreement with experimental observations. Mutants protect their colony from competitors but are themselves unable to replicate. We further show that this division of labor enhances the local competition between colonies by promoting antibiotic diversity. These results show that genomic organization can co-evolve with genomic instabilities to enable reproductive division of labor. Motivation of current workDivision of labor can evolve if trade-offs are present between different traits. To organize a division of labor, the genome architecture must evolve to enable differentiated cellular phenotypes. Cell differentiation may be coordinated through gene regulation, as occurs during embryonic development. Alternatively, when mutation rates are high, mutations themselves can guide cell and functional differentiation; however, how this evolves and is organized at the genome level remains unclear. Here, using a model of antibiotic-producing bacteria based on multicellular Streptomyces, we show that if antibiotic production trades off with replication, genome architecture can evolve to support a mutation-driven division of labor. These results are consistent with recent experimental observations and may underlie division of labor in many bacterial groups.

evolutionary biology↗

bioRxiv2020

Autocrine inhibition of cell motility can drive epithelial branching morphogenesis in 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. Surprisingly, when cultured in isolation from mesenchymal tissues, many epithelial tissues retain the ability to exhibit branching morphogenesis even in absence of proliferation. In this work, we propose a simple, experimentally-plausible mechanism that can drive branching morphogenesis in absence of proliferation and cross-talk with the surrounding mesenchymal tissue. The assumptions of our mathematical model derive from in vitro observations of the behavior of mammary epithelial cells. These data show that autocrine secretion of the growth factor TGF{beta}1 inhibits the formation of cell protrusions, leading to curvature dependent inhibition of sprouting. Our hybrid cellular Potts and partial-differential equation model correctly reproduces the experimentally observed tissue-geometry dependent determination of the sites of branching, and it suffices for the formation of self-avoiding branching structures in absence and also in presence of cell proliferation.

biophysics↗

bioRxiv2020

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. Cells can evolve their adhesion to others in a periodically changing environment, where a cells fitness solely depends on its distance from the gradient source. We show that multicellular aggregates evolve because they perform chemo-taxis more efficiently than single cells. Only when the environment changes too frequently, a unicellular state evolves which relies on cell dispersal. Both strategies prevent the invasion of the other through interference competition, creating evolutionary bi-stability. Therefore, collective behaviour can be an emergent selective driver for undifferentiated multicellularity.

evolutionary biology↗

bioRxiv2020

Computational modelling 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. Here, we present a cell-based computational model visualizing cambium activity and integrating the function of central cambium regulators. Performing iterative comparisons of plant and model anatomies, we conclude that the receptor- like kinase PXY and its ligand CLE41 are part of a minimal framework sufficient for instructing tissue organization. By integrating tissue-specific cell wall stability values, we moreover probe the influence of physical constraints on tissue geometry. Our model highlights the role of intercellular communication within the cambium and shows that a limited number of factors is sufficient to create radial growth by bidirectional tissue production. Impact statementRadial plant growth produces large parts of terrestrial biomass and can be computationally simulated with the help of an instructive framework of intercellular communication loops.

plant biology↗

bioRxiv2017

Mechanical stretching can modify the axial morphology of early chick embryos

Physical cues, experienced during early embryonic development, can influence species-specific vertebral numbers. Here we show that mechanical stretching of live chicken embryos can induce the formation of additional somites and thereby modify early segmental patterning. Stretching deforms the somites, and results in a cellular reorganization that forms stable daughter somites. Cells from the somite core thereby undergo mesenchymal-to-epithelial transitions (MET), thus meeting the geometrical demand for more border cells. Using a Cellular Potts Model, we suggest that this MET occurs through lateral induction by the existing epithelial cells. Our results indicate that self-organizing properties of the somitic mesoderm generate phenotypic plasticity that allows it to cope with variations in the mechanical environment. This plasticity may provide a novel mechanism for explaining how vertebral numbers in species may have increased during evolution. Additionally, by preventing the formation of transitional vertebrae, these self-organization qualities of somites may be selectively advantageous.

developmental biology↗