Division of Scientific Computing, Department of Information Technology, Uppsala University, 751 05, Uppsala, Sweden.
Bull Math Biol. 2019 Aug;81(8):3010-3023. doi: 10.1007/s11538-018-0454-y. Epub 2018 Jun 20.
We take up the challenge of designing realistic computational models of large interacting cell populations. The goal is essentially to bring Gillespie's celebrated stochastic methodology to the level of an interacting population of cells. Specifically, we are interested in how the gold standard of single-cell computational modeling, here taken to be spatial stochastic reaction-diffusion models, may be efficiently coupled with a similar approach at the cell population level. Concretely, we target a recently proposed set of pathways for pattern formation involving Notch-Delta signaling mechanisms. These involve cell-to-cell communication as mediated both via direct membrane contact sites and via cellular protrusions. We explain how to simulate the process in growing tissue using a multilevel approach and we discuss implications for future development of the associated computational methods.
我们接受了设计大规模相互作用细胞群体的现实计算模型的挑战。目标本质上是将 Gillespie 著名的随机方法应用于相互作用的细胞群体。具体来说,我们感兴趣的是单细胞计算建模的黄金标准(在这里被认为是空间随机反应扩散模型)如何可以有效地与细胞群体水平上的类似方法相耦合。具体来说,我们的目标是最近提出的一组涉及 Notch-Delta 信号机制的模式形成途径。这些途径涉及通过直接膜接触位点和通过细胞突起进行的细胞间通讯。我们解释了如何使用多层次方法来模拟生长组织中的这个过程,并讨论了对相关计算方法未来发展的影响。