Simpson Matthew J, Merrifield Alistair, Landman Kerry A, Hughes Barry D
Department of Mathematics and Statistics, The University of Melbourne, Victoria 3010, Australia.
Phys Rev E Stat Nonlin Soft Matter Phys. 2007 Aug;76(2 Pt 1):021918. doi: 10.1103/PhysRevE.76.021918. Epub 2007 Aug 17.
Interpretive and predictive tools are needed to assist in the understanding of cell invasion processes. Cell invasion involves cell motility and proliferation, and is central to many biological processes including developmental morphogenesis and tumor invasion. Experimental data can be collected across a wide range of scales, from the population scale to the individual cell scale. Standard continuum or discrete models used in isolation are insufficient to capture this wide range of data. We develop a discrete cellular automata model of invasion with experimentally motivated rules. The cellular automata algorithm is applied to a narrow two-dimensional lattice and simulations reveal the formation of invasion waves moving with constant speed. The simulation results are averaged in one dimension-these data are used to identify the time history of the leading edge to characterize the population-scale wave speed. This allows the relationship between the population-scale wave speed and the cell-scale parameters to be determined. This relationship is analogous to well-known continuum results for Fisher's equation. The cellular automata algorithm also produces individual cell trajectories within the invasion wave that are analogous to cell trajectories obtained with new experimental techniques. Our approach allows both the cell-scale and population-scale properties of invasion to be predicted in a way that is consistent with multiscale experimental data. Furthermore we suggest that the cellular automata algorithm can be used in conjunction with individual data to overcome limitations associated with identifying cell motility mechanisms using continuum models alone.
需要解释性和预测性工具来帮助理解细胞侵袭过程。细胞侵袭涉及细胞运动和增殖,并且是许多生物过程(包括发育形态发生和肿瘤侵袭)的核心。实验数据可以在从群体尺度到单个细胞尺度的广泛尺度上收集。单独使用的标准连续体或离散模型不足以捕获如此广泛的数据。我们开发了一个具有实验动机规则的离散细胞自动机侵袭模型。细胞自动机算法应用于一个狭窄的二维晶格,模拟揭示了以恒定速度移动的侵袭波的形成。模拟结果在一维上进行平均——这些数据用于识别前沿的时间历程,以表征群体尺度的波速。这使得能够确定群体尺度波速与细胞尺度参数之间的关系。这种关系类似于费希尔方程的著名连续体结果。细胞自动机算法还产生侵袭波内的单个细胞轨迹,这些轨迹类似于用新实验技术获得的细胞轨迹。我们的方法允许以与多尺度实验数据一致的方式预测侵袭的细胞尺度和群体尺度特性。此外,我们建议细胞自动机算法可以与个体数据结合使用,以克服仅使用连续体模型识别细胞运动机制所带来的局限性。