A stochastic model for protrusion activity

In this work we approach cell migration under a large-scale assumption, so that the system reduces to a particle in motion. Unlike classical particle models, the cell displacement results from its internal activity: the cell velocity is a function of the (discrete) protrusive forces exerted by filopodia on the substrate. Cell polarisation ability is modeled in the feedback that the cell motion exerts on the protrusion rates: faster cells form preferentially protrusions in the direction of motion. By using the mathematical framework of structured population processes previously developed to study population dynamics [Fournier and M{\'e}l{\'e}ard, 2004], we introduce rigorously the mathematical model and we derive some of its fundamental properties. We perform numerical simulations on this model showing that different types of trajectories may be obtained: Brownian-like, persistent, or intermittent when the cell switches between both previous regimes. We find back the trajectories usually described in the literature for cell migration

Numerical solutions of a 2D fluid problem coupled to a nonlinear non-local reaction-advection-diffusion problem for cell crawling migration in a discoidal domain

In this work, we present a numerical scheme for the approximate solutions of a 2D crawling cell migration problem. The model, defined on a non-deformable discoidal domain, consists in a Darcy fluid problem coupled with a Poisson problem and a reaction-advection-diffusion problem. Moreover, the advection velocity depends on boundary values, making the problem nonlinear and non local. \parFor a discoidal domain, numerical solutions can be obtained using the finite volume method on the polar formulation of the model. Simulations show that different migration behaviours can be captured

Cell migration in complex environments: chemotaxis and topographical obstacles

Cell migration is a complex phenomenon that plays an important role in many biological processes. Our aim here is to build and study models of reduced complexity to describe some aspects of cell motility in tissues. Precisely, we study the impact of some biochemical and mechanical cues on the cell dynamics in a 2D framework. For that purpose, we model the cell as an active particle with a velocity solution to a particular Stochastic Differential Equation that describes the intracellular dynamics as well as the presence of some biochemical cues. In the 1D case, an asymptotic analysis puts to light a transition between migration dominated by the cell’s internal activity and migration dominated by an external signal. In a second step, we use the contact algorithm introduced in [15,18] to describe the cell dynamics in an environment with obstacles. In the 2D case, we study how a cell submitted to a constant directional force that mimics the action of chemoattractant, behaves in the presence of obstacles. We numerically observe the existence of a velocity value that the cell can not exceed even if the directional force intensity increases. We find that this threshold value depends on the number of obstacles. Our result confirms a result that was already observed in a discrete framework in [3,4]

A Stochastic Model For Protrusion Activity

In this work we approach cell migration under a large-scale assumption, so that the system reduces to a particle in motion. Unlike classical particle models, the cell displacement results from its internal activity: the cell velocity is a function of the (discrete) protrusive forces exerted by filopodia on the substrate. Cell polarisation ability is modeled in the feedback that the cell motion exerts on the protrusion rates: faster cells form preferentially protrusions in the direction of motion. By using the mathematical framework of structured population processes previously developed to study population dynamics [4], we introduce rigorously the mathematical model and we derive some of its fundamental properties. We perform numerical simulations on this model showing that different types of trajectories may be obtained: Brownian-like, persistent, or intermittent when the cell switches between both previous regimes. We find back the trajectories usually described in the literature for cell migration

Un modèle stochastique pour l'activité de protrusion cellulaire

International audienceIn this work we approach cell migration under a large-scale assumption, so that the system reduces to a particle in motion. Unlike classical particle models, the cell displacement results from its internal activity: the cell velocity is a function of the (discrete) protrusive forces exerted by filopodia on the substrate. Cell polarisation ability is modeled in the feedback that the cell motion exerts on the protrusion rates: faster cells form preferentially protrusions in the direction of motion. By using the mathematical framework of structured population processes previously developed to study population dynamics [Fournier and Méléard, 2004], we introduce rigorously the mathematical model and we derive some of its fundamental properties. We perform numerical simulations on this model showing that different types of trajectories may be obtained: Brownian-like, persistent, or intermittent when the cell switches between both previous regimes. We find back the trajectories usually described in the literature for cell migration

A stochastic model for cell adhesion to the vascular wall

This paper deals with the adhesive interaction arising between a cell circulating in the blood flow and the vascular wall. The purpose of this work is to investigate the effect of the blood flow velocity on the cell dynamics, and in particular on its possible adhesion to the vascular wall. We formulate a model that takes into account the stochastic variability of the formation of bonds, and the influence of the cell velocity on the binding dynamics: the faster the cell goes, the more likely existing bonds are to disassemble. The model is based on a nonlinear birth-and-death-like dynamics, in the spirit of Joffe and Metivier (1986); Ethier and Kurtz (2009). We prove that, under different scaling regimes, the cell velocity follows either an ordinary differential equation or a stochastic differential equation, that we both analyse. We obtain both the identification of a shear-velocity threshold associated with the transition from cell sliding and its firm adhesion, and the expression of the cell mean stopping time as a function of its adhesive dynamics

A stochastic model for cell adhesion to the vascular wall

This paper deals with the adhesive interaction arising between a cell circulating in the blood flow and the vascular wall. The purpose of this work is to investigate the effect of the blood flow velocity on the cell dynamics, and in particular on its possible adhesion to the vascular wall. We formulate a model that takes into account the stochastic variability of the formation of bonds, and the influence of the cell velocity on the binding dynamics: the faster the cell goes, the more likely existing bonds are to disassemble. The model is based on a nonlinear birth-and-death-like dynamics, in the spirit of Joffe and Metivier (1986); Ethier and Kurtz (2009). We prove that, under different scaling regimes, the cell velocity follows either an ordinary differential equation or a stochastic differential equation, that we both analyse. We obtain both the identification of a shear-velocity threshold associated with the transition from cell sliding and its firm adhesion, and the expression of the cell mean stopping time as a function of its adhesive dynamics

Analysis of a non-local and non-linear Fokker-Planck model for cell crawling migration

Cell movement has essential functions in development, immunity and cancer. Various cell migration patterns have been reported and a general rule has recently emerged, the so-called UCSP (Universal Coupling between cell Speed and cell Persistence), [30]. This rule says that cell persistence, which quantifies the straightness of trajectories, is robustly coupled to migration speed. In [30], the advection of polarity cues by a dynamic actin cytoskeleton undergoing flows at the cellular scale was proposed as a first explanation of this universal coupling. Here, following ideas proposed in [30], we present and study a simple model to describe motility initiation in crawling cells. It consists of a non-linear and non-local Fokker-Planck equation, with a coupling involving the trace value on the boundary. In the one-dimensional case we characterize the following behaviours: solutions are global if the mass is below the critical mass, and they can blow-up in finite time above the critical mass. In addition, we prove a quantitative convergence result using relative entropy techniques

Survival criterion for a population subject to selection and mutations ; Application to temporally piecewise constant environments

International audienceWe study a parabolic Lotka-Volterra type equation that describes the evolution of a population structured by a phenotypic trait, under the effects of mutations and competition for resources modelled by a nonlocal feedback. The limit of small mutations is characterized by a Hamilton-Jacobi equation with constraint that describes the concentration of the population on some traits. This result was already established in [BP08, BMP09, LMP11] in a time-homogenous environment, when the asymptotic persistence of the population was ensured by assumptions on either the growth rate or the initial data. Here, we relax these assumptions to extend the study to situations where the population may go extinct at the limit. For that purpose, we provide conditions on the initial data for the asymptotic fate of the population. Finally, we show how this study for a time-homogenous environment allows to consider temporally piecewise constant environment

Analysis of a non-local and non-linear Fokker-Planck model for cell crawling migration

Cell movement has essential functions in development, immunity and cancer. Various cell migration patterns have been reported and a general rule has recently emerged, the so-called UCSP (Universal Coupling between cell Speed and cell Persistence), [30]. This rule says that cell persistence, which quantifies the straightness of trajectories, is robustly coupled to migration speed. In [30], the advection of polarity cues by a dynamic actin cytoskeleton undergoing flows at the cellular scale was proposed as a first explanation of this universal coupling. Here, following ideas proposed in [30], we present and study a simple model to describe motility initiation in crawling cells. It consists of a non-linear and non-local Fokker-Planck equation, with a coupling involving the trace value on the boundary. In the one-dimensional case we characterize the following behaviours: solutions are global if the mass is below the critical mass, and they can blow-up in finite time above the critical mass. In addition, we prove a quantitative convergence result using relative entropy techniques