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...
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| Format: | Article |
| Language: | English |
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Springer Nature
2008-02-01
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| Series: | Molecular Systems Biology |
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| Online Access: | https://doi.org/10.1038/msb4100204 |
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| _version_ | 1849225746981060608 |
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| author | Domitilla Del Vecchio Alexander J Ninfa Eduardo D Sontag |
| author_facet | Domitilla Del Vecchio Alexander J Ninfa Eduardo D Sontag |
| author_sort | Domitilla Del Vecchio |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-1cf80a4ae65742d0b9460a82217ff45e |
| institution | Kabale University |
| issn | 1744-4292 |
| language | English |
| publishDate | 2008-02-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj-art-1cf80a4ae65742d0b9460a82217ff45e2025-08-24T12:01:38ZengSpringer NatureMolecular Systems Biology1744-42922008-02-014111610.1038/msb4100204Modular cell biology: retroactivity and insulationDomitilla Del Vecchio0Alexander J Ninfa1Eduardo D Sontag2Department of Electrical Engineering and Computer Science, University of MichiganDepartment of Biological Chemistry, University of Michigan Medical SchoolDepartment of Mathematics, Rutgers, The State University of New JerseyAbstract 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.https://doi.org/10.1038/msb4100204feedbackinsulationmodularitysingular perturbation |
| spellingShingle | Domitilla Del Vecchio Alexander J Ninfa Eduardo D Sontag Modular cell biology: retroactivity and insulation Molecular Systems Biology feedback insulation modularity singular perturbation |
| title | Modular cell biology: retroactivity and insulation |
| title_full | Modular cell biology: retroactivity and insulation |
| title_fullStr | Modular cell biology: retroactivity and insulation |
| title_full_unstemmed | Modular cell biology: retroactivity and insulation |
| title_short | Modular cell biology: retroactivity and insulation |
| title_sort | modular cell biology retroactivity and insulation |
| topic | feedback insulation modularity singular perturbation |
| url | https://doi.org/10.1038/msb4100204 |
| work_keys_str_mv | AT domitilladelvecchio modularcellbiologyretroactivityandinsulation AT alexanderjninfa modularcellbiologyretroactivityandinsulation AT eduardodsontag modularcellbiologyretroactivityandinsulation |