Abstract
Multi-stationarity in biological systems is a mechanism of cellular decision-making. In particular, signalling pathways regulated by protein phosphorylation display features that facilitate a variety of responses to different biological inputs. The features that lead to multi-stationarity are of particular interest to determine, as well as the stability, properties of the steady states. In this paper, we determine conditions for the emergence of multi-stationarity in small motifs without feedback that repeatedly occur in signalling pathways. We derive an explicit mathematical relationship f between the concentration of a chemical species at steady state and a conserved quantity of the system such as the total amount of substrate available. We show that f determines the number of steady states and provides a necessary condition for a steady state to be stable—that is, to be biologically attainable. Further, we identify characteristics of the motifs that lead to multi-stationarity, and extend the view that multi-stationarity in signalling pathways arises from multi-site phosphorylation. Our approach relies on mass-action kinetics, and the conclusions are drawn in full generality without resorting to simulations or random generation of parameters. The approach is extensible to other systems.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Journal of the Royal Society. Interface |
| Vol/bind | 9 |
| Udgave nummer | 71 |
| Sider (fra-til) | 1224-1232 |
| Antal sider | 9 |
| ISSN | 1742-5689 |
| DOI | |
| Status | Udgivet - 7 jun. 2012 |