Programming Juxtacrine-Based Synthetic Signaling Networks in a Cellular Potts Framework

Synthetic development is a synthetic biology subfield aiming to reprogram higher-order eukaryotic cells for tissue formation and morphogenesis. Reprogramming efforts commonly rely upon implementing custom signaling networks into these cells, but the efficient design of these signaling networks is a substantial challenge. It is difficult to predict the tissue/morphogenic outcome of these networks, and in vitro testing of many networks is both costly and time-consuming. We therefore developed a computational framework with an in silico cell line (ISCL) that sports basic but modifiable features such as adhesion, motility, growth, and division. More importantly, ISCL can be quickly engineered with custom genetic circuits to test, improve, and explore different signaling network designs. We implemented this framework in a free cellular Potts modeling software CompuCell3D. In this chapter, we briefly discuss how to start with CompuCell3D and then go through the steps of how to make and modify ISCL. We then go through the steps of programming custom genetic circuits into ISCL to generate an example signaling network.