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Nonlinear signalling networks and cell-to-cell variability transform external signals into broadly distributed or bimodal responses
Date Issued
2014-06-25
Date Available
2016-07-07T15:00:41Z
Abstract
We show theoretically and experimentally a mechanism behind the emergence of wide or bimodal protein distributions in biochemical networks with nonlinear input–output characteristics (the dose–response curve) and variability in protein abundance. Large cell-to-cell variation in the nonlinear dose–response characteristics can be beneficial to facilitate two distinct groups of response levels as opposed to a graded response. Under the circumstances that we quantify mathematically, the two distinct responses can coexist within a cellular population, leading to the emergence of a bimodal protein distribution. Using flow cytometry, we demonstrate the appearance of wide distributions in the hypoxia-inducible factor-mediated response network in HCT116 cells. With help of our theoretical framework, we perform a novel calculation of the magnitude of cell-to-cell heterogeneity in the dose–response obtained experimentally.
Sponsorship
European Commission - Seventh Framework Programme (FP7)
Science Foundation Ireland
Type of Material
Journal Article
Publisher
The Royal Society
Journal
Interface
Volume
11
Issue
98
Copyright (Published Version)
2014 the Authors
Language
English
Status of Item
Peer reviewed
This item is made available under a Creative Commons License
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Owning collection
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