Integrating Intracellular Dynamics Using CompuCell3D and Bionetsolver: Applications to Multiscale Modelling of Cancer Cell Growth and Invasion
Integrating Intracellular Dynamics Using CompuCell3D and Bionetsolver: Applications to Multiscale Modelling of Cancer Cell Growth and Invasion
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DOI：
10.1371/journal.pone.0033726
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发表时间：
2012-03-26
期刊：
影响因子：
3.7
通讯作者：
Chaplain, Mark A. J.
中科院分区：
文献类型：
--
作者：
Andasari, Vivi;Roper, Ryan T.;Chaplain, Mark A. J.
在本文中，我们提出了一个多尺度的，基于个人的模拟环境，集成了CompuCell 3D的细胞水平上的基于格子的建模和Bionetsolver的细胞内建模。CompuCell 3D或CC 3D提供了基于格子的Cellular Potts模型或CPM（也称为Glazier-Graner-Hogeweg或GGH模型）的实现，以及基于大都会算法的Monte Carlo方法，用于系统演化。将细胞系统的CC 3D与亚细胞系统的Bionetsolver相结合，使我们能够开发一个多尺度数学模型，并研究由于细胞内部动力学而导致的细胞行为的演变，捕获细胞行为和相互作用的各个方面，这是使用连续统方法不可能实现的。然后，我们将这种多尺度建模技术应用于癌症生长和侵袭的模型，该模型基于Ramis-Conde et al.（2008）先前发表的模型，其中单个细胞行为由描述E-钙粘蛋白和β-连环蛋白动力学的分子网络驱动。在这个模型中，我们称之为基于中心的模型，一种替代的基于个人的建模技术，即，一个无网格的方法。在许多方面，GGH或CPM方法和基于中心的模型的方法具有相同的总体目标，即模拟生物细胞的行为和相互作用。虽然这两种方法的数学基础和计算实现是非常不同的，所提出的模拟的结果是相互兼容的，这表明通过使用基于个人的方法，我们可以制定一个自然的方式来描述复杂的多细胞，多尺度模型。从模型交叉验证的角度来看，使用替代方法轻松再现一种建模方法的结果的能力也是必不可少的，并且还有助于识别特定于给定计算方法的任何建模伪像。
In this paper we present a multiscale, individual-based simulation environment that integrates CompuCell3D for lattice-based modelling on the cellular level and Bionetsolver for intracellular modelling. CompuCell3D or CC3D provides an implementation of the lattice-based Cellular Potts Model or CPM (also known as the Glazier-Graner-Hogeweg or GGH model) and a Monte Carlo method based on the metropolis algorithm for system evolution. The integration of CC3D for cellular systems with Bionetsolver for subcellular systems enables us to develop a multiscale mathematical model and to study the evolution of cell behaviour due to the dynamics inside of the cells, capturing aspects of cell behaviour and interaction that is not possible using continuum approaches. We then apply this multiscale modelling technique to a model of cancer growth and invasion, based on a previously published model of Ramis-Conde et al. (2008) where individual cell behaviour is driven by a molecular network describing the dynamics of E-cadherin and beta-catenin. In this model, which we refer to as the centre-based model, an alternative individual-based modelling technique was used, namely, a lattice-free approach. In many respects, the GGH or CPM methodology and the approach of the centre-based model have the same overall goal, that is to mimic behaviours and interactions of biological cells. Although the mathematical foundations and computational implementations of the two approaches are very different, the results of the presented simulations are compatible with each other, suggesting that by using individual-based approaches we can formulate a natural way of describing complex multi-cell, multiscale models. The ability to easily reproduce results of one modelling approach using an alternative approach is also essential from a model cross-validation standpoint and also helps to identify any modelling artefacts specific to a given computational approach.