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Cascading signaling pathways improve the fidelity of a stochastically and deterministically simulated molecular RS latch

BACKGROUND: While biological systems have often been compared with digital systems, they differ by the strong effect of crosstalk between signals due to diffusivity in the medium, reaction kinetics and geometry. Memory elements have allowed the creation of autonomous digital systems and although bio...

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Detalles Bibliográficos
Autores principales: Mills, Evan, Truong, Kevin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3225856/
https://www.ncbi.nlm.nih.gov/pubmed/19615050
http://dx.doi.org/10.1186/1752-0509-3-72
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author Mills, Evan
Truong, Kevin
author_facet Mills, Evan
Truong, Kevin
author_sort Mills, Evan
collection PubMed
description BACKGROUND: While biological systems have often been compared with digital systems, they differ by the strong effect of crosstalk between signals due to diffusivity in the medium, reaction kinetics and geometry. Memory elements have allowed the creation of autonomous digital systems and although biological systems have similar properties of autonomy, equivalent memory mechanisms remain elusive. Any such equivalent memory system, however, must silence the effect of crosstalk to maintain memory fidelity. RESULTS: Here, we present a system of enzymatic reactions that behaves like an RS latch (a simple memory element in digital systems). Using both a stochastic molecular simulator and ordinary differential equation simulator, we showed that crosstalk between two latches operating in the same spatial localization disrupts the memory fidelity of both latches. Crosstalk was reduced or silenced when simple reaction loops were replaced with multiple step or cascading reactions, showing that cascading signaling pathways are less susceptible to crosstalk. CONCLUSION: Thus, the common biological theme of cascading signaling pathways is advantageous for maintaining the fidelity of a memory latch in the presence of crosstalk. The experimental implementation of such a latch system will lead to novel approaches to cell control using synthetic proteins and will contribute to our understanding of why cells behave differently even when given the same stimulus.
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spelling pubmed-32258562011-11-30 Cascading signaling pathways improve the fidelity of a stochastically and deterministically simulated molecular RS latch Mills, Evan Truong, Kevin BMC Syst Biol Research Article BACKGROUND: While biological systems have often been compared with digital systems, they differ by the strong effect of crosstalk between signals due to diffusivity in the medium, reaction kinetics and geometry. Memory elements have allowed the creation of autonomous digital systems and although biological systems have similar properties of autonomy, equivalent memory mechanisms remain elusive. Any such equivalent memory system, however, must silence the effect of crosstalk to maintain memory fidelity. RESULTS: Here, we present a system of enzymatic reactions that behaves like an RS latch (a simple memory element in digital systems). Using both a stochastic molecular simulator and ordinary differential equation simulator, we showed that crosstalk between two latches operating in the same spatial localization disrupts the memory fidelity of both latches. Crosstalk was reduced or silenced when simple reaction loops were replaced with multiple step or cascading reactions, showing that cascading signaling pathways are less susceptible to crosstalk. CONCLUSION: Thus, the common biological theme of cascading signaling pathways is advantageous for maintaining the fidelity of a memory latch in the presence of crosstalk. The experimental implementation of such a latch system will lead to novel approaches to cell control using synthetic proteins and will contribute to our understanding of why cells behave differently even when given the same stimulus. BioMed Central 2009-07-17 /pmc/articles/PMC3225856/ /pubmed/19615050 http://dx.doi.org/10.1186/1752-0509-3-72 Text en Copyright ©2009 Mills and Truong; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Mills, Evan
Truong, Kevin
Cascading signaling pathways improve the fidelity of a stochastically and deterministically simulated molecular RS latch
title Cascading signaling pathways improve the fidelity of a stochastically and deterministically simulated molecular RS latch
title_full Cascading signaling pathways improve the fidelity of a stochastically and deterministically simulated molecular RS latch
title_fullStr Cascading signaling pathways improve the fidelity of a stochastically and deterministically simulated molecular RS latch
title_full_unstemmed Cascading signaling pathways improve the fidelity of a stochastically and deterministically simulated molecular RS latch
title_short Cascading signaling pathways improve the fidelity of a stochastically and deterministically simulated molecular RS latch
title_sort cascading signaling pathways improve the fidelity of a stochastically and deterministically simulated molecular rs latch
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3225856/
https://www.ncbi.nlm.nih.gov/pubmed/19615050
http://dx.doi.org/10.1186/1752-0509-3-72
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