Design and implementation of a biomolecular circuit for tracking protein concentration

This paper describes the design, modeling, synthesis and preliminary validation of a protein concentration regulator circuit. The circuit is designed to maintain the level of a target protein to a reference level, specified by the amount of another protein. This is implemented using a single negative feedback loop that inhibits the production of the target protein once its concentration is equal to the reference amount. A mathematical model consisting of a set of ODEs is derived from mass action laws and Hill function approximations of protein production. Steady-state analysis of the model is used to predict parameter sensitivity and experimental behavior. We implemented this circuit in E. coli using scaffold-based sequestration and transcriptional activation. Preliminary experimental results show the system matching predictions from our model and performing the expected task.