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Molecular Titration Promotes Oscillations and Bistability in Minimal Network Models with Monomeric Regulators

Cuba Samaniego, Christian; Giordano, Giulia LU ; Kim, Jongmin; Blanchini, Franco and Franco, Elisa (2016) In ACS Synthetic Biology 5(4). p.321-333
Abstract

Molecular titration is emerging as an important biochemical interaction mechanism within synthetic devices built with nucleic acids and the CRISPR/Cas system. We show that molecular titration in the context of feedback circuits is a suitable mechanism to enhance the emergence of oscillations and bistable behaviors. We consider biomolecular modules that can be inhibited or activated by input monomeric regulators; the regulators compete with constitutive titrating species to determine the activity of their target. By tuning the titration rate and the concentration of titrating species, it is possible to modulate the delay and convergence speed of the transient response, and the steepness and dead zone of the stationary response of the... (More)

Molecular titration is emerging as an important biochemical interaction mechanism within synthetic devices built with nucleic acids and the CRISPR/Cas system. We show that molecular titration in the context of feedback circuits is a suitable mechanism to enhance the emergence of oscillations and bistable behaviors. We consider biomolecular modules that can be inhibited or activated by input monomeric regulators; the regulators compete with constitutive titrating species to determine the activity of their target. By tuning the titration rate and the concentration of titrating species, it is possible to modulate the delay and convergence speed of the transient response, and the steepness and dead zone of the stationary response of the modules. These phenomena favor the occurrence of oscillations when modules are interconnected to create a negative feedback loop; bistability is favored in a positive feedback interconnection. Numerical simulations are supported by mathematical analysis showing that the capacity of the closed loop systems to exhibit oscillations or bistability is structural.

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Please use this url to cite or link to this publication:
author
publishing date
type
Contribution to journal
publication status
published
subject
keywords
bistability, delays, monomeric regulator, oscillations, RNA, synthetic biology, titration
in
ACS Synthetic Biology
volume
5
issue
4
pages
13 pages
publisher
American Chemical Society (ACS)
external identifiers
  • scopus:84966397026
DOI
10.1021/acssynbio.5b00176
language
English
LU publication?
no
id
02fcb711-3438-4624-87fb-1deaa22ec2e9
date added to LUP
2016-07-06 15:06:48
date last changed
2017-11-05 05:05:10
@article{02fcb711-3438-4624-87fb-1deaa22ec2e9,
  abstract     = {<p>Molecular titration is emerging as an important biochemical interaction mechanism within synthetic devices built with nucleic acids and the CRISPR/Cas system. We show that molecular titration in the context of feedback circuits is a suitable mechanism to enhance the emergence of oscillations and bistable behaviors. We consider biomolecular modules that can be inhibited or activated by input monomeric regulators; the regulators compete with constitutive titrating species to determine the activity of their target. By tuning the titration rate and the concentration of titrating species, it is possible to modulate the delay and convergence speed of the transient response, and the steepness and dead zone of the stationary response of the modules. These phenomena favor the occurrence of oscillations when modules are interconnected to create a negative feedback loop; bistability is favored in a positive feedback interconnection. Numerical simulations are supported by mathematical analysis showing that the capacity of the closed loop systems to exhibit oscillations or bistability is structural.</p>},
  author       = {Cuba Samaniego, Christian and Giordano, Giulia and Kim, Jongmin and Blanchini, Franco and Franco, Elisa},
  keyword      = {bistability,delays,monomeric regulator,oscillations,RNA,synthetic biology,titration},
  language     = {eng},
  month        = {04},
  number       = {4},
  pages        = {321--333},
  publisher    = {American Chemical Society (ACS)},
  series       = {ACS Synthetic Biology},
  title        = {Molecular Titration Promotes Oscillations and Bistability in Minimal Network Models with Monomeric Regulators},
  url          = {http://dx.doi.org/10.1021/acssynbio.5b00176},
  volume       = {5},
  year         = {2016},
}