Bifurcations and multistability in inducible three-gene toggle switch networks

Fuente: arXiv
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Main Authors: Rousseau, Rebecca J., Phillips, Rob
Format: Preprint
Published: 2025
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author Rousseau, Rebecca J.
Phillips, Rob
author_facet Rousseau, Rebecca J.
Phillips, Rob
contents Control of transcription presides over a vast array of biological processes, including those mediated by gene regulatory circuits that exhibit multistability. Within these circuits, two- and three-gene network motifs are particularly critical to the repertoire of metabolic and developmental pathways. Theoretical models of these circuits, however, often vary parameters such as dissociation constants, transcription rates, and degradation rates without specifying precisely how these parameters are controlled biologically. In this study, we examine the role of effector molecules, which can alter the concentrations of the active transcription factors that control regulation, and are ubiquitous in regulatory processes across many biological settings. We specifically consider allosteric regulation in the context of extending the standard bistable switch to three-gene networks, and explore the rich multistable dynamics exhibited in these architectures as a function of effector concentrations. We then analyze how the dynamics evolve under various interpretations of regulatory circuit mechanics, underlying inducer activity, and perturbations thereof. Notably, the biological mechanism by which we model effector control over dual-function proteins transforms not only the phenotypic trend of dynamic tuning but also the set of available dynamic regimes. In this way, we determine key parameters and regulatory features that drive phenotypic decisions, and offer an experimentally tunable structure for encoding inducible multistable behavior arising from both single and dual-function allosteric transcription factors.
format Preprint
id arxiv_https___arxiv_org_abs_2509_24926
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle Bifurcations and multistability in inducible three-gene toggle switch networks
Rousseau, Rebecca J.
Phillips, Rob
Molecular Networks
Biological Physics
Subcellular Processes
Control of transcription presides over a vast array of biological processes, including those mediated by gene regulatory circuits that exhibit multistability. Within these circuits, two- and three-gene network motifs are particularly critical to the repertoire of metabolic and developmental pathways. Theoretical models of these circuits, however, often vary parameters such as dissociation constants, transcription rates, and degradation rates without specifying precisely how these parameters are controlled biologically. In this study, we examine the role of effector molecules, which can alter the concentrations of the active transcription factors that control regulation, and are ubiquitous in regulatory processes across many biological settings. We specifically consider allosteric regulation in the context of extending the standard bistable switch to three-gene networks, and explore the rich multistable dynamics exhibited in these architectures as a function of effector concentrations. We then analyze how the dynamics evolve under various interpretations of regulatory circuit mechanics, underlying inducer activity, and perturbations thereof. Notably, the biological mechanism by which we model effector control over dual-function proteins transforms not only the phenotypic trend of dynamic tuning but also the set of available dynamic regimes. In this way, we determine key parameters and regulatory features that drive phenotypic decisions, and offer an experimentally tunable structure for encoding inducible multistable behavior arising from both single and dual-function allosteric transcription factors.
title Bifurcations and multistability in inducible three-gene toggle switch networks
topic Molecular Networks
Biological Physics
Subcellular Processes
url https://arxiv.org/abs/2509.24926