Pattern Formation and Bistability in a Synthetic Intercellular\nGenetic Toggle

Differentiation\nwithin multicellular organisms is a complex process\nthat helps to establish spatial patterning and tissue formation within\nthe body. Often, the differentiation of cells is governed by morphogens\nand intercellular signaling molecules that guide the fate of each\ncell, frequently using toggle-like regulatory components. Synthetic\nbiologists have long sought to recapitulate patterned differentiation\nwith engineered cellular communities, and various methods for differentiating\nbacteria have been invented. Here, we couple a synthetic corepressive\ntoggle switch with intercellular signaling pathways to create a “quorum-sensing\ntoggle”. We show that this circuit not only exhibits population-wide\nbistability in a well-mixed liquid environment but also generates\npatterns of differentiation in colonies grown on agar containing an\nexternally supplied morphogen. If coupled to other metabolic processes,\ncircuits such as the one described here would allow for the engineering\nof spatially patterned, differentiated bacteria for use in biomaterials\nand bioelectronics.