The theory of monotone dynamical systems has been found very useful in the modeling of some gene, protein, and signaling networks.
In monotone systems, every net feedback loop is positive. On the other hand, negative feedback loops are important features
of many systems, since they are required for adaptation and precision. This paper shows that, provided that these negative
loops act at a comparatively fast time scale, the main dynamical property of (strongly) monotone systems, convergence to steady
states, is still valid. An application is worked out to a double-phosphorylation “futile cycle” motif which plays a central
role in eukaryotic cell signaling.
Keywords Singular perturbation - Monotone systems - Asymptotic stability - MAPK system
Mathematics Subject Classification (2000) 34D15 - 37C65