Middleton Alistair M, Fleck Christian, Grima Ramon
University of Heidelberg, Im Neuenheimer Feld 267, 69120 Heidelberg, Germany; Center for Biological Systems Analysis, University of Freiburg, Habsburgerstr. 49, 79104 Freiburg, Germany.
Laboratory for Systems and Synthetic Biology, Dreijenplein 10, 6703HB Wageningen, The Netherlands.
J Theor Biol. 2014 Oct 21;359:220-32. doi: 10.1016/j.jtbi.2014.06.011. Epub 2014 Jun 24.
Cell-cell adhesion plays a key role in the collective migration of cells and in determining correlations in the relative cell positions and velocities. Recently, it was demonstrated that off-lattice individual cell based models (IBMs) can accurately capture the correlations observed experimentally in a migrating cell population. However, IBMs are often computationally expensive and difficult to analyse mathematically. Traditional continuum-based models, in contrast, are amenable to mathematical analysis and are computationally less demanding, but typically correspond to a mean-field approximation of cell migration and so ignore cell-cell correlations. In this work, we address this problem by using an off-lattice IBM to derive a continuum approximation which does take into account correlations. We furthermore show that a mean-field approximation of the off-lattice IBM leads to a single partial integro-differential equation of the same form as proposed by Sherratt and co-workers to model cell adhesion. The latter is found to be only effective at approximating the ensemble averaged cell number density when mechanical interactions between cells are weak. In contrast, the predictions of our novel continuum model for the time-evolution of the ensemble cell number density distribution and of the density-density correlation function are in close agreement with those obtained from the IBM for a wide range of mechanical interaction strengths. In particular, we observe 'front-like' propagation of cells in simulations using both our IBM and our continuum model, but not in the continuum model simulations obtained using the mean-field approximation.
细胞间黏附在细胞的集体迁移以及确定相对细胞位置和速度的相关性方面起着关键作用。最近,有研究表明,基于非晶格单个细胞的模型(IBMs)能够准确捕捉在迁移细胞群体中通过实验观察到的相关性。然而,基于个体细胞的模型通常计算成本高昂且难以进行数学分析。相比之下,传统的基于连续介质的模型易于进行数学分析且计算要求较低,但通常对应于细胞迁移的平均场近似,因此忽略了细胞间的相关性。在这项工作中,我们通过使用非晶格基于个体细胞的模型来推导一种连续介质近似方法,该方法确实考虑了相关性,从而解决了这个问题。我们还表明,基于个体细胞的模型的平均场近似会导致一个与Sherratt及其同事提出的用于模拟细胞黏附的形式相同的单个偏积分 - 微分方程。结果发现,当细胞间的机械相互作用较弱时,后者仅在近似总体平均细胞数密度方面有效。相比之下,我们新颖的连续介质模型对于总体细胞数密度分布的时间演化以及密度 - 密度相关函数的预测,在广泛的机械相互作用强度范围内与基于个体细胞的模型所获得的预测结果非常吻合。特别是,我们在使用我们的基于个体细胞模型和连续介质模型的模拟中都观察到了细胞的“前沿状”传播,但在使用平均场近似得到的连续介质模型模拟中却没有观察到。