Bottom-up construction of in vitro switchable memories

Reaction networks displaying bistability provide a chemical mechanism for long-term memory storage in cells, as exemplified by many epigenetic switches. These biological systems are not only bistable but switchable, in the sense that they can be flipped from one state to the other by application of...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 109; no. 47; pp. E3212 - E3220
Main Authors Padirac, Adrien, Fujii, Teruo, Rondelez, Yannick
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 20.11.2012
National Acad Sciences
SeriesPNAS Plus
Subjects
Biological Sciences
Cells
Deoxyribonucleic acid
DNA
DNA - genetics
DNA - metabolism
Epigenetics
Feedback, Physiological
Gene Regulatory Networks
Genes, Switch
Memory
Models, Genetic
PNAS Plus
synthetic biology
Templates, Genetic
topology
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Summary:Reaction networks displaying bistability provide a chemical mechanism for long-term memory storage in cells, as exemplified by many epigenetic switches. These biological systems are not only bistable but switchable, in the sense that they can be flipped from one state to the other by application of specific molecular stimuli. We have reproduced such functions through the rational assembly of dynamic reaction networks based on basic DNA biochemistry. Rather than rewiring genetic systems as synthetic biology does in vivo, our strategy consists of building simplified dynamic analogs in vitro, in an artificial, well-controlled milieu. We report successively a bistable system, a two-input switchable memory element, and a single-input push-push memory circuit. These results suggest that it is possible to build complex time-responsive molecular circuits by following a modular approach to the design of dynamic in vitro behaviors. Our approach thus provides an unmatched opportunity to study topology/function relationships within dynamic reaction networks.
Bibliography:http://dx.doi.org/10.1073/pnas.1212069109
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Edited by David A. Tirrell, California Institute of Technology, Pasadena, CA, and approved October 2, 2012 (received for review July 14, 2012)
Author contributions: A.P. and Y.R. designed research; A.P. performed research; T.F. contributed new reagents/analytic tools; A.P. and Y.R. analyzed data; and A.P. and Y.R. wrote the paper.
ISSN:0027-8424
1091-6490
1091-6490
DOI:10.1073/pnas.1212069109