论文标题
一种混合离散 - 胞源方法,用于建模图灵模式形成
A hybrid discrete-continuum approach to model Turing pattern formation
论文作者
论文摘要
自1952年引入以来,图灵(Turing)的(前)模式理论(“形态发生的化学基础”)已被广泛应用于发育生物学的许多领域。相关的模式形成模型通常构成了相互作用化学物种(“形态剂”)的反应扩散方程系统的系统,其在某些空间结构域中的异质分布充当了细胞的模板,以形成某种模式或结构,例如,通过化学预先图案引起的分化或扩散。在这里,我们开发了一种通过图灵机制形成细胞模式的混合离散式建模框架。在此框架中,将基于随机的个体的细胞运动和增殖模型与某些形态浓度的反应扩散系统结合使用。作为一个说明性的例子,我们专注于一个模型,在该模型中,形态剂的动力学由激活剂抑制剂系统支配,从而引起图灵预绘制。然后,细胞通过两种形式的化学依赖性细胞作用中的任何一种与局部区域中的形态剂相互作用:趋化性和化学控制的增殖。我们首先考虑在静态空间结构域上构成的这种混合模型,然后转向生长域的情况。在这两种情况下,我们都正式得出相应的确定性连续性极限,并表明当考虑到足够多的细胞时,由随机个体基于基于个体的模型产生的空间模式与其确定性连续性对应物之间存在极好的定量匹配。本文旨在为建模框架基础的思想提供概念证明,以便将相关方法应用于未来特定图案和形态学过程的研究。
Since its introduction in 1952, Turing's (pre-)pattern theory ("the chemical basis of morphogenesis") has been widely applied to a number of areas in developmental biology. The related pattern formation models normally comprise a system of reaction-diffusion equations for interacting chemical species ("morphogens"), whose heterogeneous distribution in some spatial domain acts as a template for cells to form some kind of pattern or structure through, for example, differentiation or proliferation induced by the chemical pre-pattern. Here we develop a hybrid discrete-continuum modelling framework for the formation of cellular patterns via the Turing mechanism. In this framework, a stochastic individual-based model of cell movement and proliferation is combined with a reaction-diffusion system for the concentrations of some morphogens. As an illustrative example, we focus on a model in which the dynamics of the morphogens are governed by an activator-inhibitor system that gives rise to Turing pre-patterns. The cells then interact with morphogens in their local area through either of two forms of chemically-dependent cell action: chemotaxis and chemically-controlled proliferation. We begin by considering such a hybrid model posed on static spatial domains, and then turn to the case of growing domains. In both cases, we formally derive the corresponding deterministic continuum limit and show that that there is an excellent quantitative match between the spatial patterns produced by the stochastic individual-based model and its deterministic continuum counterpart, when sufficiently large numbers of cells are considered. This paper is intended to present a proof of concept for the ideas underlying the modelling framework, with the aim to then apply the related methods to the study of specific patterning and morphogenetic processes in the future.