An ultrasensitive motif for robust closed loop control of biomolecular systems

We describe a molecular reaction network that can be used to achieve robust closed loop control in synthetic biology. The network relies on a motif that exhibits an ultrasensitive input-output mapping, and is therefore termed “Brink Controller”. Ultrasensitivity is achieved by combining molecular titration and an activation/deactivation cycle, and requires the presence of fast titration and switching rates, together with slow degradation rates. We propose to use two Brink Controllers in parallel to overcome a major limitation in traditional molecular feedback controllers: their inability to supply simultaneously positive and negative action on the system to be controlled. The Brink Controller motif can be used to achieve both regulatory functions, by simply swapping the inputs of the motif. We assess the effectiveness of the closed loop architecture with numerical simulations, and we suggest potential experimental realizations of the circuit.