Nonlinear signalling networks and cell-to-cell variability transform external signals into broadly distributed or bimodal responses
Data(s) |
25/06/2014
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Resumo |
We show theoretically and experimentally a mechanismbehind 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. © 2014 The Author(s) Published by the Royal Society. All rights reserved. |
Formato |
application/pdf application/pdf |
Identificador |
http://eprints.aston.ac.uk/26133/1/Supplementary_material.pdf Dobrzyński, Maciej; Nguyen, Lan K.; Birtwistle, Marc R.; von Kriegsheim, Alexander; Fernández, Alfonso Blanco; Cheong, Alex; Kolch, Walter and Kholodenko, Boris N. (2014). Nonlinear signalling networks and cell-to-cell variability transform external signals into broadly distributed or bimodal responses. Journal of the Royal Society Interface, 11 (98), |
Relação |
http://eprints.aston.ac.uk/26133/ |
Tipo |
Article PeerReviewed |