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无格子细胞侵润模型:离散模拟与行波。

Lattice-free models of cell invasion: discrete simulations and travelling waves.

机构信息

Department of Mathematics and Statistics, University of Canterbury, Christchurch, New Zealand,

出版信息

Bull Math Biol. 2013 Nov;75(11):2150-66. doi: 10.1007/s11538-013-9885-7. Epub 2013 Aug 17.

Abstract

Invasion waves of cells play an important role in development, disease, and repair. Standard discrete models of such processes typically involve simulating cell motility, cell proliferation, and cell-to-cell crowding effects in a lattice-based framework. The continuum-limit description is often given by a reaction-diffusion equation that is related to the Fisher-Kolmogorov equation. One of the limitations of a standard lattice-based approach is that real cells move and proliferate in continuous space and are not restricted to a predefined lattice structure. We present a lattice-free model of cell motility and proliferation, with cell-to-cell crowding effects, and we use the model to replicate invasion wave-type behaviour. The continuum-limit description of the discrete model is a reaction-diffusion equation with a proliferation term that is different from lattice-based models. Comparing lattice-based and lattice-free simulations indicates that both models lead to invasion fronts that are similar at the leading edge, where the cell density is low. Conversely, the two models make different predictions in the high-density region of the domain, well behind the leading edge. We analyse the continuum-limit description of the lattice-based and lattice-free models to show that both give rise to invasion wave type solutions that move with the same speed but have very different shapes. We explore the significance of these differences by calibrating the parameters in the standard Fisher-Kolmogorov equation using data from the lattice-free model. We conclude that estimating parameters using this kind of standard procedure can produce misleading results.

摘要

细胞入侵波在发育、疾病和修复中起着重要作用。此类过程的标准离散模型通常涉及在基于格子的框架中模拟细胞运动、细胞增殖和细胞间拥挤效应。连续体极限描述通常由反应扩散方程给出,该方程与 Fisher-Kolmogorov 方程有关。标准格子方法的一个局限性是,真实细胞在连续空间中移动和增殖,而不受预定义格子结构的限制。我们提出了一种具有细胞间拥挤效应的无格子细胞运动和增殖模型,并使用该模型复制了入侵波型行为。离散模型的连续体极限描述是一个具有增殖项的反应扩散方程,与基于格子的模型不同。基于格子和无格子模拟的比较表明,这两种模型都导致在细胞密度较低的前沿处具有相似的入侵前沿。相反,这两种模型在前沿后面的高密度区域做出了不同的预测。我们分析了基于格子和无格子模型的连续体极限描述,表明这两种模型都产生了以相同速度移动但形状非常不同的入侵波型解。我们通过使用无格子模型的数据来校准标准 Fisher-Kolmogorov 方程中的参数来探讨这些差异的意义。我们得出的结论是,使用这种标准程序估计参数可能会产生误导性结果。

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