Engineering Principles in Bio-molecular Systems: From Retroactivity to Modularity *

Modularity plays a fundamental role in the prediction of the behavior of a system from the behavior of its components, guaranteeing that the properties of individual components do not change upon interconnection. Just as electrical, hydraulic, and other physical systems often do not display modularity, nor do many biochemical systems, and specifically, genetic, and signaling networks. Here, we study the effect of interconnections on the input/output dynamic characteristics of transcriptional components, focusing on a concept, which we call “retroactivity” that plays a role similar to impedance in electrical circuits. In order to attenuate the effect of retroactivity on a system dynamics, we propose to design insulation devices based on a feedback mechanism inspired by the design of amplifiers in electronics. In particular, we introduce a bio-molecular realization of an insulation device based on phosphorylation.*