Programmable Fusion and Differentiation of Synthetic Minimal Cells

Nathaniel J Gaut, Jose Gomez-Garcia, Joseph M Heili, Brock Cash, Qiyuan Han, Aaron E Engelhart, Katarzyna P Adamala

ACS Synth. Biol. 2022, 11, 2, 855–866

Synthetic cells can mimic the intricate complexities of live cells, while mitigating the level of noise that is present natural systems; however, many crucial processes still need to be demonstrated in synthetic cells to use them to comprehensively study and engineer biology. Here we demonstrate key functionalities of synthetic cells previously available only to natural life: differentiation and mating. This work presents a toolset for engineering combinatorial genetic circuits in synthetic cells. We demonstrate how progenitor populations can differentiate into new lineages in response to small molecule stimuli or as a result of fusion, and we provide practical demonstration of utility for metabolic engineering. This work provides a tool for bioengineering and for natural pathway studies, as well as paving the way toward the construction of live artificial cells.