Institute of Epigenetics and Stem Cells, Helmholtz Zentrum München; München, Germany.
Institute of Functional Epigenetics, Helmholtz Zentrum München; Neuherberg, Germany.
PLoS Comput Biol. 2022 Mar 14;18(3):e1009552. doi: 10.1371/journal.pcbi.1009552. eCollection 2022 Mar.
Cells can measure shallow gradients of external signals to initiate and accomplish a migration or a morphogenetic process. Recently, starting from mathematical models like the local-excitation global-inhibition (LEGI) model and with the support of empirical evidence, it has been proposed that cellular communication improves the measurement of an external gradient. However, the mathematical models that have been used have over-simplified geometries (e.g., they are uni-dimensional) or assumptions about cellular communication, which limit the possibility to analyze the gradient sensing ability of more complex cellular systems. Here, we generalize the existing models to study the effects on gradient sensing of cell number, geometry and of long- versus short-range cellular communication in 2D systems representing epithelial tissues. We find that increasing the cell number can be detrimental for gradient sensing when the communication is weak and limited to nearest neighbour cells, while it is beneficial when there is long-range communication. We also find that, with long-range communication, the gradient sensing ability improves for tissues with more disordered geometries; on the other hand, an ordered structure with mostly hexagonal cells is advantageous with nearest neighbour communication. Our results considerably extend the current models of gradient sensing by epithelial tissues, making a step further toward predicting the mechanism of communication and its putative mediator in many biological processes.
细胞可以测量外部信号的浅层梯度，从而启动和完成迁移或形态发生过程。最近，从局部兴奋全局抑制（LEGI）模型等数学模型出发，并得到经验证据的支持，人们提出细胞通讯可以改善对外界梯度的测量。然而，所使用的数学模型简化了几何形状（例如，它们是一维的）或对细胞通讯的假设，这限制了分析更复杂细胞系统的梯度感应能力的可能性。在这里，我们将现有的模型推广到 2D 系统中，以研究细胞数量、几何形状以及长程与短程细胞通讯对上皮组织中梯度感应的影响。我们发现，当通讯较弱且仅限于最近邻细胞时，增加细胞数量可能会对梯度感应产生不利影响，而当存在长程通讯时，增加细胞数量则有益。我们还发现，对于具有更多无序几何形状的组织，长程通讯可以提高梯度感应能力；另一方面，具有大多数六边形细胞的有序结构在与最近邻通讯时是有利的。我们的结果极大地扩展了上皮组织中梯度感应的现有模型，为预测许多生物学过程中的通讯机制及其潜在介质迈出了一步。
