No Arabic abstract
The aim of this paper is to further develop mathematical models for bleb formation in cells, including cell-membrane interactions with linker proteins. This leads to nonlinear reaction-diffusion equations on a surface coupled to fluid dynamics in the bulk. We provide a detailed mathematical analysis and investigate some singular limits of the model, connecting it to previous literature. Moreover, we provide numerical simulations in different scenarios, confirming that the model can reproduce experimental results on bleb initation.
We introduce and analyze several aspects of a new model for cell differentiation. It assumes that differentiation of progenitor cells is a continuous process. From the mathematical point of view, it is based on partial differential equations of transport type. Specifically, it consists of a structured population equation with a nonlinear feedback loop. This models the signaling process due to cytokines, which regulate the differentiation and proliferation process. We compare the continuous model to its discrete counterpart, a multi-compartmental model of a discrete collection of cell subpopulations recently proposed by Marciniak-Czochra et al. in 2009 to investigate the dynamics of the hematopoietic system. We obtain uniform bounds for the solutions, characterize steady state solutions, and analyze their linearized stability. We show how persistence or extinction might occur according to values of parameters that characterize the stem cells self-renewal. We also perform numerical simulations and discuss the qualitative behavior of the continuous model vis a vis the discrete one.
We study a mathematical model describing the dynamics of a pluripotent stem cell population involved in the blood production process in the bone marrow. This model is a differential equation with a time delay. The delay describes the cell cycle duration and is uniformly distributed on an interval. We obtain stability conditions independent of the delay. We also show that the distributed delay can destabilize the entire system. In particularly, it is shown that Hopf bifurcations can occur.
We consider density solutions for gradient flow equations of the form $u_t = abla cdot ( gamma(u) abla mathrm N(u))$, where $mathrm N$ is the Newtonian repulsive potential in the whole space $mathbb R^d$ with the nonlinear convex mobility $gamma(u)=u^alpha$, and $alpha>1$. We show that solutions corresponding to compactly supported initial data remain compactly supported for all times leading to moving free boundaries as in the linear mobility case $gamma(u)=u$. For linear mobility it was shown that there is a special solution in the form of a disk vortex of constant intensity in space $u=c_1t^{-1}$ supported in a ball that spreads in time like $c_2t^{1/d}$, thus showing a discontinuous leading front or shock. Our present results are in sharp contrast with the case of concave mobilities of the form $gamma(u)=u^alpha$, with $0<alpha<1$ studied in [9]. There, we developed a well-posedness theory of viscosity solutions that are positive everywhere and moreover display a fat tail at infinity. Here, we also develop a well-posedness theory of viscosity solutions that in the radial case leads to a very detail analysis allowing us to show a waiting time phenomena. This is a typical behavior for nonlinear degenerate diffusion equations such as the porous medium equation. We will also construct explicit self-similar solutions exhibiting similar vortex-like behaviour characterizing the long time asymptotics of general radial solutions under certain assumptions. Convergent numerical schemes based on the viscosity solution theory are proposed analysing their rate of convergence. We complement our analytical results with numerical simulations ilustrating the proven results and showcasing some open problems.
In the development of multiscale biological models it is crucial to establish a connection between discrete microscopic or mesoscopic stochastic models and macroscopic continuous descriptions based on cellular density. In this paper a continuous limit of a two-dimensional Cellular Potts Model (CPM) with excluded volume is derived, describing cells moving in a medium and reacting to each other through both direct contact and long range chemotaxis. The continuous macroscopic model is obtained as a Fokker-Planck equation describing evolution of the cell probability density function. All coefficients of the general macroscopic model are derived from parameters of the CPM and a very good agreement is demonstrated between CPM Monte Carlo simulations and numerical solution of the macroscopic model. It is also shown that in the absence of contact cell-cell interactions, the obtained model reduces to the classical macroscopic Keller-Segel model. General multiscale approach is demonstrated by simulating spongy bone formation from loosely packed mesenchyme via the intramembranous route suggesting that self-organizing physical mechanisms can account for this developmental process.
Recent biological research has sought to understand how biochemical signaling pathways, such as the mitogen-activated protein kinase (MAPK) family, influence the migration of a population of cells during wound healing. Fishers Equation has been used extensively to model experimental wound healing assays due to its simple nature and known traveling wave solutions. This partial differential equation with independent variables of time and space cannot account for the effects of biochemical activity on wound healing, however. To this end, we derive a structured Fishers Equation with independent variables of time, space, and biochemical pathway activity level and prove the existence of a self-similar traveling wave solution to this equation. We also consider a more complicated model with different phenotypes based on MAPK activation and numerically investigate how various temporal patterns of biochemical activity can lead to increased and decreased rates of population migration.