arXiv subjects

Camille Pouchol

Publications and source records attributed to Camille Pouchol.

25 records · Page 2Linked to original sources

arXiv2018

A chemotaxis-based explanation of spheroid formation in 3D cultures of breast cancer cells

Three-dimensional cultures of cells are gaining popularity as an in vitro improvement over 2D Petri dishes. In many such experiments, cells have been found to organize in aggregates. We present new results of three-dimensional in vitro cultures of breast cancer cells exhibiting patterns. Understanding their formation is of particular interest in the context of cancer since metastases have been shown to be created by cells moving in clusters. In this paper, we propose that the main mechanism which leads to the emergence of patterns is chemotaxis, i.e., oriented movement of cells towards high concentration zones of a signal emitted by the cells themselves. Studying a Keller-Segel PDE system to model chemotactical auto-organization of cells, we prove that it is subject to Turing instability under a time-dependent condition. This result is illustrated by two-dimensional simulations of the model showing spheroidal patterns. They are qualitatively compared to the biological results and their variability is discussed both theoretically and numerically.

q-bio.CB↗

arXiv2018

Energy and implicit discretization of the Fokker-Planck and Keller-Segel type equations

The parabolic-elliptic Keller-Segel equation with sensitivity saturation, because of its pattern formation ability, is a challenge for numerical simulations. We provide two finite-volume schemes whose goals are to preserve, at the discrete level, the fundamental properties of the solutions, namely energy dissipation, steady states, positivity and conservation of total mass. These requirements happen to be critical when it comes to distinguishing between discrete steady states, Turing unstable transient states, numerical artifacts or approximate steady states as obtained by a simple upwind approach. These schemes are obtained either by following closely the gradient flow structure or by a proper exponential rewriting inspired by the Scharfetter-Gummel discretization. An interesting feature is that upwind is also necessary for all the expected properties to be preserved at the semi-discrete level. These schemes are extended to the fully discrete level and this leads us to tune precisely the terms according to explicit or implicit discretizations. Using some appropriate monotony properties (reminiscent of the maximum principle), we prove well-posedness for the scheme as well as all the other requirements. Numerical implementations and simulations illustrate the respective advantages of the three methods we compare.

math.NA↗

arXiv2018

Phase portrait control for 1D monostable and bistable reaction-diffusion equations

We consider the problem of controlling parabolic semilinear equations arising in population dynamics, either in finite time or infinite time. These are the monostable and bistable equations on $(0,L)$ for a density of individuals $0 \leq y(t,x) \leq 1$, with Dirichlet controls taking their values in $[0,1]$. We prove that the system can never be steered to extinction (steady state $0$) or invasion (steady state $1$) in finite time, but is asymptotically controllable to $1$ independently of the size $L$, and to $0$ if the length $L$ of the interval domain is less than some threshold value $L^\star$, which can be computed from transcendental integrals. In the bistable case, controlling to the other homogeneous steady state $0 <θ< 1$ is much more intricate. We rely on a staircase control strategy to prove that $θ$ can be reached in finite time if and only if $L< L^\star$. The phase plane analysis of those equations is instrumental in the whole process. It allows us to read obstacles to controllability, compute the threshold value for domain size as well as design the path of steady states for the control strategy.

math.OC↗

arXiv2018

Combination of direct methods and homotopy in numerical optimal control: application to the optimization of chemotherapy in cancer

We consider a state-constrained optimal control problem of a system of two non-local partial-differential equations, which is an extension of the one introduced in a previous work in mathematical oncology. The aim is to minimize the tumor size through chemotherapy while avoiding the emergence of resistance to the drugs. The numerical approach to solve the problem was the combination of direct methods and continuation on discretization parameters, which happen to be insufficient for the more complicated model, where diffusion is added to account for mutations. In the present paper, we propose an approach relying on changing the problem so that it can theoretically be solved thanks to a Pontryagin Maximum Principle in infinite dimension. This provides an excellent starting point for a much more reliable and efficient algorithm combining direct methods and continuations. The global idea is new and can be thought of as an alternative to other numerical optimal control techniques.

math.OC↗

arXiv2018

On the stability of the state 1 in the non-local Fisher-KPP equation in bounded domains

We consider the non-local Fisher-KPP equation on a bounded domain with Neu-mann boundary conditions. Thanks to a Lyapunov function, we prove that under a general hypothesis on the Kernel involved in the non-local term, the homogenous steady state 1 is globally asymptotically stable. This assumption happens to be linked to some conditions given in the literature, which ensure that travelling waves link 0 to 1.

math.AP↗

arXiv2017

Global stability with selection in integro-differential Lotka-Volterra systems modelling trait-structured populations

We analyse the asymptotic behaviour of integro-differential equations modelling $N$ populations in interaction, all structured by different traits. Interactions are modelled by non-local terms involving linear combinations of the total number of individuals in each population. These models have already been shown to be suitable for the modelling of drug resistance in cancer, and they generalise the usual Lotka-Volterra ordinary differential equations. Our aim is to give conditions under which there is persistence of all species. Through the analysis of a Lyapunov function, our first main result gives a simple and general condition on the matrix of interactions, together with a convergence rate. The second main result establishes another type of condition in the specific case of mutualistic interactions. When either of these conditions is met, we describe which traits are asymptotically selected.

q-bio.PE↗

arXiv2016

Asymptotic analysis and optimal control of an integro-differential system modelling healthy and cancer cells exposed to chemotherapy

We consider a system of two coupled integro-differential equations modelling populations of healthy and cancer cells under therapy. Both populations are structured by a phenotypic variable, representing their level of resistance to the treatment. We analyse the asymptotic behaviour of the model under constant infusion of drugs. By designing an appropriate Lyapunov function, we prove that both densities converge to Dirac masses. We then define an optimal control problem, by considering all possible infusion protocols and minimising the number of cancer cells over a prescribed time frame. We provide a quasi-optimal strategy and prove that it solves this problem for large final times. For this modelling framework, we illustrate our results with numerical simulations, and compare our optimal strategy with periodic treatment schedules.

math.OC↗