Modular Cell Biology: Retroactivity and Insulation

Domitilla Del Vecchio
Assistant Professor
Electrical Engineering and Computer Science EECS
University of Michigan, Ann Arbor

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 networks. Here, we study the effect of interconnections on the input/ output dynamic haracteristics of transcriptional components, focusing on a property, which we call "retroactivity," that plays a role similar to impedance in electrical circuits. In transcriptional networks, retroactivity is large when the amount of transcription factor is comparable to, or smaller than, the amount of promoter binding sites, or when the affinity of such binding sites is high. In order to attenuate the effect of retroactivity, we propose to design insulation devices based on a feedback mechanism inspired by the design of amplifiers in electronics. We introduce a bio-molecular realization of an insulation device based on a phosphorylation/dephosphorylation mechanism. This mechanism enjoys a remarkable insulation property, due to the fast time scales of the phosphorylation and dephosphorylation reactions. We briefly argue how the faster time scale of a device with respect to its input can be viewed as a general insulation mechanism peculiar of bio-molecular systems.

Finally, numerical results are presented to investigate the effect of the high gains of the proposed insulator design on biological noise and a design tradeoff is highlighted.