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Author Notes:

Corresponding Author: ilya.nemenman@emory.edu

We thank Rustom Antia, Lily Chylek, William Hlavacek, Andre Levchenko, Andrew Mugler, Dmitry Shayakhmetov, and Veronika Zarnitsyna for useful discussions.

Subjects:

Research Funding:

This work was supported in part by the James S. McDonnell Foundation grant 220020321 and by the National Science Foundation grants IOS-1208126 and PoLS-1410978.

Keywords:

  • Science & Technology,
  • Life Sciences & Biomedicine
  • Biochemical Research Methods
  • Mathematical & Computational Biology
  • Biochemistry & Molecular Biology
  • SIGNAL-TRANSDUCTION
  • ANTAGONISM
  • SPECIFICITY
  • SENSITIVITY
  • MECHANISM
  • PATHWAYS
  • MODEL
  • DISCRIMINATION
  • INFORMATION
  • TOLERANCE

Simple biochemical networks allow accurate sensing of multiple ligands with a single receptor

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Journal Title:

PLoS Computational Biology

Volume:

Volume 13, Number 4

Publisher:

, Pages e1005490-e1005490

Type of Work:

Article | Final Publisher PDF

Abstract:

Cells use surface receptors to estimate concentrations of external ligands. Limits on the accuracy of such estimations have been well studied for pairs of ligand and receptor species. However, the environment typically contains many ligands, which can bind to the same receptors with different affinities, resulting in cross-talk. In traditional rate models, such cross-talk prevents accurate inference of concentrations of individual ligands. In contrast, here we show that knowing the precise timing sequence of stochastic binding and unbinding events allows one receptor to provide information about multiple ligands simultaneously and with a high accuracy. We show that such high-accuracy estimation of multiple concentrations can be realized with simple structural modifications of the familiar kinetic proofreading biochemical network diagram. We give two specific examples of such modifications. We argue that structural and functional features of real cellular biochemical sensory networks in immune cells, such as feedforward and feedback loops or ligand antagonism, sometimes can be understood as solutions to the accurate multi-ligand estimation problem.

Copyright information:

© 2017 Singh, Nemenman.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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