Biology subjects

Rappel, W.-J.

Publications and source records attributed to Rappel, W.-J..

7 recordsLinked to original sources

bioRxiv2025

Single-cell chiral symmetry breaking under confinement

Single cells confined by the extracellular matrix can exhibit persistent rotational motion, yet the physical mechanisms underlying this chiral symmetry breaking remain unclear. Here, we address this gap with a cellular phase field model that couples cell deformation, cell polarization governed by stochastic excitable dynamics, and confinement. We identify the confinement strength as a bifurcation parameter determining three regimes: strong confinement prevents rotation through spatial constraints, intermediate confinement induces stochastic transitions between chiral and non-chiral states, and weak confinement allows persistent rotational motion. For the intermediate regime, we develop a semi-Markovian renewal process framework that characterizes the stochastic dynamics through dwell time statistics, transition probabilities and first-passage times. For the weak confinement regime, we reveal that a mechanochemical feedback enables coherent rotations despite internal noise through the reduction of local excitability mediated by mechanical contraction. We formalize this feedback analytically using Kramers escape theory. Experiments on epithelial MCF10A cells in Matrigel validate predictions for the weak confinement regime. Our results establish a theoretical approach for understanding single-cell chiral symmetry breaking under confinement, with implications for controlling single-cell dynamics by tuning extracellular matrix properties.

biophysics↗

bioRxiv2025

Coupling Step-Wise Motility and Traction Force Patterns in chemotaxing cells

Chemotaxing Dictyostelium discoideum cells migrate in a step-wise fashion characterized by periodic protrusion, contraction, and rear retraction cycles accompanied by distinct traction force patterns. Traction force microscopy reveals two stationary force spots that exchange identity as the cell advances and generate a convergent stress pattern with both axial and lateral components. To investigate the physical origin of these traction patterns, we developed a continuum, phase-field model that couples cytosolic flow, active stresses, and substrate friction within a cell with a deformable morpholgy. The model incorporates protrusive forces at the front, contractile stresses at the rear and sides, and spatially localized adhesive regions that undergo cyclic activation. While this baseline model reproduces persistent motion, it fails to capture the experimentally observed traction force patterns and cell morphology. Guided by new experiments visualizing myosin dynamics, we extended the model to include a localized contractile myosin patch positioned between the two adhesive regions. This modification yields cell shapes, speeds, and convergent traction patterns consistent with experimental measurements. The results demonstrate that a centrally positioned myosin patch is sufficient to generate the step-wise migration cycle and the characteristic convergent traction pattern of Dictyostelium cells, providing a mechanistic link between intracellular contractility, cytosolic flow, and force transmission during amoeboid motility.

biophysics↗

bioRxiv2023

Eukaryotic chemotaxis under periodic stimulation shows temporal gradient dependence

When cells of the social amoeba Dictyostelium discoideum are starved of nutrients they start to synthesize and secrete the chemical messenger and chemoattractant cyclic Adenosine Mono Phosphate (cAMP). This signal is relayed by other cells, resulting in the establishment of periodic waves. The cells aggregate through chemotaxis towards the center of these waves. We investigated the chemotactic response of individual cells to repeated exposure to waves of cAMP generated by a microfluidic device. When the period of the waves is short, the chemotactic ability of the cells was found to increase upon exposure to more waves, suggesting the development of a longer-term memory. This effect was not significant for longer wave periods. We show that the experimental results are consistent with a model that includes a slowly rising and decaying component that is activated by the temporal gradient of cAMP concentration. The observed enhancement in chemotaxis is relevant to populations in the wild: once sustained, periodic waves of the chemoattractant are established, it is beneficial to cells to improve their chemotactic ability in order to reach the aggregation center sooner.

biophysics↗

bioRxiv2021

BoolSim, a Graphical Interface for Open Access Boolean Network Simulations and Use in Guard Cell CO2 Signaling

Signaling networks are at the heart of almost all biological processes. Most of these networks contain a large number of components and often the connections between these components are either not known, or the rate equations that govern the dynamics of soluble signaling components are not quantified. This uncertainty in network topology and parameters can make it challenging to formulate detailed mathematical models. Boolean networks, in which all components are either on or off, have emerged as viable alternatives to more detailed mathematical models but can be difficult to implement. Therefore, open source format of such models for community use is desirable. Here we present BoolSim, a freely available graphical user interface (GUI) that allows users to easily construct and analyze Boolean networks. BoolSim can be applied to any Boolean network. We demonstrate BoolSims application using a previously published network for abscisic acid-driven stomatal closure in Arabidopsis. We also show how BoolSim can be used to generate testable predictions by extending the network to include CO2 regulation of stomatal movements. Predictions of the model were experimentally tested and the model was iteratively modified based on experiments showing that ABA closes stomata even at near zero CO2 concentrations (1.5 ppm CO2). One Sentence SummaryThis study presents an open-source, graphical interface for the simulation of Boolean networks and applies it to an abscisic acid signaling network in guard cells, extended to include input from CO2.

plant biology↗

bioRxiv2020

Tissue topography steers migrating Drosophila border cells

Moving cells can sense and respond to physical features of the microenvironment, however in vivo the significance of tissue topography is mostly unknown. Here we use the Drosophila border cells, an established model for in vivo cell migration, to study how chemical and physical information influence migration path selection. Live imaging, genetics, modeling, and simulations show that, although chemical cues were thought to be sufficient, microtopography is also important. Chemoattractants promote predominantly posterior movement, whereas tissue architecture presents orthogonal information, a path of least resistance concentrated near the center of the egg chamber. E-cadherin supplies a permissive haptotactic cue. Our results provide insight into how cells integrate and prioritize topographical, adhesive, and chemoattractant cues to choose one path amongst many.

developmental biology↗

bioRxiv2019

Plasticity of cell migration resulting from mechanochemical coupling

Eukaryotic cells can migrate using different modes, ranging from amoeboid-like, during which actin filled protrusions come and go, to keratocyte-like, characterized by a stable morphology and persistent motion. How cells can switch between these modes is still not well understood but waves of signaling events on the cell cortex are thought to play an important role in these transitions. Here we present a simple two component biochemical reaction-diffusion model based on relaxation oscillators and couple this to a model for the mechanics of cell deformations. Different migration modes, including amoeboid-like and keratocyte-like, naturally emerge through phase transitions determined by interactions between biochemical traveling waves, cell mechanics and morphology. The model predictions are explicitly verified by systematically reducing the protrusive force of the actin network in experiments using wild-type Dictyostelium discoideum cells. Our results indicate the importance of coupling signaling events to cell mechanics and morphology and may be applicable in a wide variety of cell motility systems.

biophysics↗

bioRxiv2019

Flower-like patterns in multi-species biofilms

Diverse interactions among species within bacterial biofilms often lead to intricate spatiotemporal dynamics. The spatial structure of biofilms can determine growth and survival of different species, but the mechanisms driving formation of this structure are not fully understood. Here, we describe the emergence of complex structures in a biofilm grown from mixtures of motile and non-motile bacterial species on a soft agar surface. Time-lapse imaging shows that non-motile bacteria "hitchhike" on the motile bacteria as the latter migrate outward. The non-motile bacteria accumulate at the boundary of the colony and trigger an instability that leaves behind striking flower-like patterns. The mechanism of the front instability governing this pattern formation is elucidated by a mathematical model for the frictional motion of the colony interface, with friction depending on the local concentration of the nonmotile species along the interface. A more elaborate two-dimensional phase-field model that explicitly accounts for the interplay between growth, mechanical stress from the motile species, and friction provided by the non-motile species, fully reproduces the observed flower-like patterns.

microbiology↗