title: Modular cell biology: retroactivity and insulation.
abstract: 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 characteristics of transcriptional components, focusing on a property, which we call 'retroactivity', that plays a role analogous to non-zero output impedance in electrical systems. 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. To attenuate the effect of retroactivity, we propose a feedback mechanism inspired by the design of amplifiers in electronics. We introduce, in particular, a mechanism based on a phosphorylation-dephosphorylation cycle. This mechanism enjoys a remarkable insulation property, due to the fast timescales of the phosphorylation and dephosphorylation reactions.
authors.affiliation: Department of Electrical Engineering and Computer Science, University of Michigan, Ann Arbor, MI 48109, USA. ddv@umich.edu
authors.forename: Domitilla
authors.initials: D
authors.lastname: Del Vecchio
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Ninfa
authors.forename: Eduardo D
authors.initials: ED
authors.lastname: Sontag
mesh_terms: D000818:Animals; D001665:Binding Sites; D001695:Biology; D003198:Computer Simulation; D005246:Feedback; D006801:Humans; D053858:Metabolic Networks and Pathways / Q000235:genetics; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008954:Models, Biological; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction; D049490:Systems Biology; D014157:Transcription Factors; D014158:Transcription, Genetic
chemical_list: D014157:Transcription Factors; D020928:Mitogen-Activated Protein Kinases