Hartmann Dirk, Miura Takashi
Institute of Applied Mathematics, University of Heidelberg, Im Neuenheimer Feld 294, 69120 Heidelberg, Germany.
J Theor Biol. 2006 Oct 21;242(4):862-72. doi: 10.1016/j.jtbi.2006.05.009. Epub 2006 May 19.
It has been shown experimentally that lung epithelial explants have an ability to undergo branching morphogenesis without mesenchyme. However, the mechanisms of this phenomenon remain to be elucidated. In the present study, we construct a mathematical model that can reproduce the dynamics of in vitro branching morphogenesis. We show that the system is essentially governed by three variables--c(0) which is the initial fibroblast growth factor (FGF) concentration, D which is the diffusion coefficient of FGF, and beta which describes the mechanical strength of the cytoskeleton. It is confirmed by numerical simulations that this model can reproduce the experimentally obtained patterns qualitatively. Finally, we experimentally verify two predictions from the model: effects of very high FGF concentration and effects of small mechanical contributions of the cytoskeleton. The theoretical predictions match well with the experimental results.
实验表明,肺上皮外植体在没有间充质的情况下具有进行分支形态发生的能力。然而,这一现象的机制仍有待阐明。在本研究中,我们构建了一个能够重现体外分支形态发生动力学的数学模型。我们表明,该系统主要由三个变量控制——c(0),即初始成纤维细胞生长因子(FGF)浓度;D,即FGF的扩散系数;以及β,它描述了细胞骨架的机械强度。通过数值模拟证实,该模型能够定性地重现实验获得的模式。最后,我们通过实验验证了模型的两个预测:极高FGF浓度的影响和细胞骨架微小机械贡献的影响。理论预测与实验结果吻合良好。