Department of Biosciences, Rice University, Houston, Texas 77005, United States.
Department of Mathematics, University of Houston, Houston, Texas 77204, United States.
ACS Synth Biol. 2024 Sep 20;13(9):2844-2860. doi: 10.1021/acssynbio.4c00272. Epub 2024 Aug 30.
Differentiation within multicellular organisms is a complex process that helps to establish spatial patterning and tissue formation within the body. Often, the differentiation of cells is governed by morphogens and intercellular signaling molecules that guide the fate of each cell, frequently using toggle-like regulatory components. Synthetic biologists have long sought to recapitulate patterned differentiation with engineered cellular communities, and various methods for differentiating bacteria have been invented. Here, we couple a synthetic corepressive toggle switch with intercellular signaling pathways to create a "quorum-sensing toggle". We show that this circuit not only exhibits population-wide bistability in a well-mixed liquid environment but also generates patterns of differentiation in colonies grown on agar containing an externally supplied morphogen. If coupled to other metabolic processes, circuits such as the one described here would allow for the engineering of spatially patterned, differentiated bacteria for use in biomaterials and bioelectronics.
多细胞生物的分化是一个复杂的过程，有助于在体内建立空间模式和组织形成。通常，细胞的分化受形态发生素和细胞间信号分子的控制，这些分子指导每个细胞的命运，经常使用类似于开关的调节组件。合成生物学家长期以来一直试图用工程化的细胞群落来重现有模式的分化，并且已经发明了各种用于分化细菌的方法。在这里，我们将一个合成的核心抑制性开关与细胞间信号通路相耦合，创建了一个“群体感应开关”。我们表明，该电路不仅在充分混合的液体环境中表现出全种群双稳态，而且在含有外部供应形态发生素的琼脂上生长的菌落中也产生了分化模式。如果与其他代谢过程相结合，如本文所述的电路可以用于工程化具有空间图案的、分化的细菌，用于生物材料和生物电子学。
