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
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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