Influence of time-scale separation  on sensitivity and robustness of interlinked positive feedback loops

Interlinked positive feedback loops are an acknowledged motif ubiquitous in the design and regulation of biological functions. They typically achieve switch-like behavior in response to an external stimulus. The conjunction of a slow and a fast loop have been observed to simultaneously  achieve sensitivity and robustness. We investigated the dynamic mechanisms underlying this remarkable property. Using slow-fast decomposition and explicit multiscale analysis of the dynamics, we show that its main origin lies in incomplete bifurcations and stabilization of nonequilibrium states, while the amplitude of the stimulus plays only a marginal role. The identification of the different time scales of the regulatory network dynamics is thus central to a proper understanding of the system response and behavior. An open question we are now addressing is the influence of interlinking architecture, controlling for instance the asymmetry between on-off and off-on transitions as well as the response to various kinds of noise.  Joint work with Marc-Thorsten Hütt (Jacobs University, Bremen, Germany)

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