A major goal in synthetic development is to build gene regulatory circuits that control patterning. In natural development, an interplay between mechanical and chemical communication shapes the dynamics of multicellular gene regulatory circuits. For synthetic circuits, how non-genetic properties of the growth environment impact circuit behavior remains poorly explored. Here, we first describe an occurrence of mechano-chemical coupling in synthetic Notch (synNotch) patterning circuits: high cell density decreases synNotch-gated gene expression in different cellular systems in vitro. We then construct, both in vitro and in silico, a synNotch-based signal propagation circuit whose outcome can be regulated by cell density. Spatial and temporal patterning outcomes of this circuit can be predicted and controlled via modulation of cell proliferation, initial cell density, and/or spatial distribution of cell density. Our work demonstrates that synthetic patterning circuit outcome can be controlled via cellular growth, providing a means for programming multicellular circuit patterning outcomes.

合成开发的一个主要目标是构建控制模式的基因调控回路。在自然发育中，机械和化学通讯之间的相互作用塑造了多细胞基因调控回路的动力学。对于合成电路，生长环境的非遗传特性如何影响电路行为的研究仍然很少。在这里，我们首先描述了合成 Notch （synNotch） 图案电路中机械化学偶联的发生：高细胞密度降低了体外不同细胞系统中 synNotch 门控基因的表达。然后，我们在体外和计算机中构建了一个基于 synNotch 的信号传播电路，其结果可以由细胞密度调节。可以通过调节细胞增殖、初始细胞密度和/或细胞密度的空间分布来预测和控制该电路的空间和时间模式结果。我们的工作表明，合成图案化电路结果可以通过细胞生长来控制，为多细胞电路图案化结果提供了一种编程方法。