Nonlinear signalling networks and cell-to-cell variability transform external signals into broadly distributed or bimodal responses

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Title: Nonlinear signalling networks and cell-to-cell variability transform external signals into broadly distributed or bimodal responses
Authors: Dobrzyński, Maciej
Nguyen, Lan K.
Birtwistle, Marc R.
Kriegsheim, Alexander von
Fernández, Alfonso Blanco
Cheong, Alex
Kolch, Walter
Kholodenko, Boris N.
Permanent link: http://hdl.handle.net/10197/7762
Date: 25-Jun-2014
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.
Funding Details: European Commission - Seventh Framework Programme (FP7)
Science Foundation Ireland
Type of material: Journal Article
Publisher: The Royal Society
Copyright (published version): 2014 the Authors
Keywords: Bimodality;Cell heterogeneity;Dose–response;Signalling networks
DOI: 10.1098/rsif.2014.0383
Language: en
Status of Item: Peer reviewed
Appears in Collections:Conway Institute Research Collection
SBI Research Collection
Medicine Research Collection

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