dorsal/arxiv
View SchemaThe stochastic behavior of a molecular switching circuit with feedback
| Authors | Supriya Krishnamurthy, Eric Smith, David Krakauer, Walter Fontana |
|---|---|
| Categories | |
| ArXiv ID | q-bio/0312020 |
| URL | https://arxiv.org/abs/q-bio/0312020 |
| Journal | Biology Direct, 2:13 (2007) |
Abstract
Background: Using a statistical physics approach, we study the stochastic switching behavior of a model circuit of multisite phosphorylation and dephosphorylation with feedback. The circuit consists of a kinase and phosphatase acting on multiple sites of a substrate that, contingent on its modification state, catalyzes its own phosphorylation and, in a symmetric scenario, dephosphorylation. The symmetric case is viewed as a cartoon of conflicting feedback that could result from antagonistic pathways impinging on the state of a shared component. Results: Multisite phosphorylation is sufficient for bistable behavior under feedback even when catalysis is linear in substrate concentration, which is the case we consider. We compute the phase diagram, fluctuation spectrum and large-deviation properties related to switch memory within a statistical mechanics framework. Bistability occurs as either a first-order or second-order non-equilibrium phase transition, depending on the network symmetries and the ratio of phosphatase to kinase numbers. In the second-order case, the circuit never leaves the bistable regime upon increasing the number of substrate molecules at constant kinase to phosphatase ratio. Conclusions: The number of substrate molecules is a key parameter controlling both the onset of the bistable regime, fluctuation intensity, and the residence time in a switched state. The relevance of the concept of memory depends on the degree of switch symmetry, as memory presupposes information to be remembered, which is highest for equal residence times in the switched states. Reviewers: This article was reviewed by Artem Novozhilov (nominated by Eugene Koonin), Sergei Maslov, and Ned Wingreen.
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"abstract": "Background: Using a statistical physics approach, we study the stochastic\nswitching behavior of a model circuit of multisite phosphorylation and\ndephosphorylation with feedback. The circuit consists of a kinase and\nphosphatase acting on multiple sites of a substrate that, contingent on its\nmodification state, catalyzes its own phosphorylation and, in a symmetric\nscenario, dephosphorylation. The symmetric case is viewed as a cartoon of\nconflicting feedback that could result from antagonistic pathways impinging on\nthe state of a shared component.\n Results: Multisite phosphorylation is sufficient for bistable behavior under\nfeedback even when catalysis is linear in substrate concentration, which is the\ncase we consider. We compute the phase diagram, fluctuation spectrum and\nlarge-deviation properties related to switch memory within a statistical\nmechanics framework. Bistability occurs as either a first-order or second-order\nnon-equilibrium phase transition, depending on the network symmetries and the\nratio of phosphatase to kinase numbers. In the second-order case, the circuit\nnever leaves the bistable regime upon increasing the number of substrate\nmolecules at constant kinase to phosphatase ratio.\n Conclusions: The number of substrate molecules is a key parameter controlling\nboth the onset of the bistable regime, fluctuation intensity, and the residence\ntime in a switched state. The relevance of the concept of memory depends on the\ndegree of switch symmetry, as memory presupposes information to be remembered,\nwhich is highest for equal residence times in the switched states.\n Reviewers: This article was reviewed by Artem Novozhilov (nominated by Eugene\nKoonin), Sergei Maslov, and Ned Wingreen.",
"arxiv_id": "q-bio/0312020",
"authors": [
"Supriya Krishnamurthy",
"Eric Smith",
"David Krakauer",
"Walter Fontana"
],
"categories": [
"q-bio.MN",
"cond-mat.stat-mech"
],
"journal_ref": "Biology Direct, 2:13 (2007)",
"title": "The stochastic behavior of a molecular switching circuit with feedback",
"url": "https://arxiv.org/abs/q-bio/0312020"
},
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