Recent synthetic biology experiments reveal that signaling modules designed to target cell–cell adhesion enable self-organization of multicellular structures Toda etal (2018 Science 361 156–162). Changes in homotypic adhesion that arise through contact-dependent signaling networks result in sorting of an aggregate into two- or three-layered structures. Here we investigate the formation, maintenance, and robustness of such self-organization in the context of a computational model. To do so, we use an established model for Notch/ligand signaling within cells to set up differential E-cadherin expression. This signaling model is integrated with the cellular Potts model to track state changes, adhesion, and cell sorting in a group of cells. The resulting multicellular structures are in accordance with those observed in the experimental reference. In addition to reproducing these experimental results, we track the dynamics of the evolving structures and cell states to understand how such morphologies are dynamically maintained. This appears to be an important developmental principle that was not emphasized in previous models. Our computational model facilitates more detailed understanding of the link between intra- and intercellular signaling, spatio-temporal rearrangement, and emergent behavior at the scale of hundred(s) of cells.

最近的合成生物学实验表明，旨在靶向细胞间粘附的信号模块能够实现多细胞结构的自组织 Toda et al (2018 Science 361156–162)。通过依赖于接触的信号网络产生的同型粘附的变化导致聚集体分类成两层或三层结构。在这里，我们在计算模型的背景下研究这种自组织的形成、维护和鲁棒性。为此，我们使用已建立的细胞内缺口/配体信号模型来建立差异 E-钙粘蛋白表达。该信号模型与细胞 Potts 模型集成，以跟踪一组细胞中的状态变化、粘附和细胞分选。所得多细胞结构与实验参考中观察到的一致。除了重现这些实验结果外，我们还跟踪进化结构和细胞状态的动态，以了解这些形态是如何动态保持的。这似乎是一个重要的发展原则，在以前的模型中没有强调。我们的计算模型有助于更详细地了解细胞内和细胞间信号、时空重排和数百个细胞规模的紧急行为之间的联系。