A Modular Computational Framework for the Rational Design and Exploration of Synthetic Development

SUMMARY Synthetic development is a nascent field of research that uses the tools of synthetic biology to design genetic programs directing cellular patterning and morphogenesis in higher eukaryotic cells, mainly mammalian ones. Current design methods of these genetic programs proceed inefficiently, relying on trial and error processes. By contrast, computational models can act as rapid testing platforms, revealing the networks, signals, and responses required for achieving robust target structures. We introduce a computational model where contact dependent cell-cell signaling networks and cellular responses can be chosen in a modular fashion, allowing in silico recreation of known synthetic morphogenic trajectories such as those resulting in multilayered synthetic spheroids. By altering the modular components, our model also allows for the exploration of new trajectories that can result in hollowed, elongated, and oscillatory structures. Our model functions as a testing ground illuminating how synthetic biology tools can be used to create particular structures. In addition, it can provide valuable insight into our understanding of both imagined and extant cellular morphologies.