Zhai Xiaoling, Larkin Joseph W, Süel Gürol M, Mugler Andrew
Department of Physics and Astronomy, Purdue University, West Lafayette, Indiana.
Department of Biology and Department of Physics, Boston University, Boston, Massachusetts.
Biophys J. 2020 Apr 7;118(7):1721-1732. doi: 10.1016/j.bpj.2020.02.007. Epub 2020 Feb 26.
Many multicellular communities propagate signals in a directed manner via excitable waves. Cell-to-cell heterogeneity is a ubiquitous feature of multicellular communities, but the effects of heterogeneity on wave propagation are still unclear. Here, we use a minimal FitzHugh-Nagumo-type model to investigate excitable wave propagation in a two-dimensional heterogeneous community. The model shows three dynamic regimes in which waves either propagate directionally, die out, or spiral indefinitely, and we characterize how these regimes depend on the heterogeneity parameters. We find that in some parameter regimes, spatial correlations in the heterogeneity enhance directional propagation and suppress spiraling. However, in other regimes, spatial correlations promote spiraling, a surprising feature that we explain by demonstrating that these spirals form by a second, distinct mechanism. Finally, we characterize the dynamics using techniques from percolation theory. Despite the fact that percolation theory does not completely describe the dynamics quantitatively because it neglects the details of the excitable propagation, we find that it accounts for the transitions between the dynamic regimes and the general dependency of the spiral period on the heterogeneity and thus provides important insights. Our results reveal that the spatial structure of cell-to-cell heterogeneity can have important consequences for signal propagation in cellular communities.
许多多细胞群落通过可兴奋波以定向方式传播信号。细胞间的异质性是多细胞群落普遍存在的特征,但异质性对波传播的影响仍不清楚。在这里,我们使用一个最小的FitzHugh-Nagumo型模型来研究二维异质群落中的可兴奋波传播。该模型显示了三种动态状态,即波要么定向传播、消失,要么无限螺旋,并且我们描述了这些状态如何依赖于异质性参数。我们发现,在某些参数范围内,异质性中的空间相关性增强了定向传播并抑制了螺旋。然而,在其他范围内,空间相关性促进了螺旋,这是一个令人惊讶的特征,我们通过证明这些螺旋是由第二种不同的机制形成来解释。最后,我们使用渗流理论技术来描述动力学。尽管渗流理论由于忽略了可兴奋传播的细节而不能完全定量地描述动力学,但我们发现它解释了动态状态之间的转变以及螺旋周期对异质性的一般依赖性,从而提供了重要的见解。我们的结果表明,细胞间异质性的空间结构可能对细胞群落中的信号传播产生重要影响。