Robust network topologies for temperature-inducible bioswitches

BACKGROUND: Thermoinducible bioswitches are unique in that the all-or-none switch response is triggered by temperature, which is a global factor that impacts all biochemical reaction processes. To date, temperature-inducible bioswitches rely exclusively on special thermal sensing biomolecules of DNA, RNA, proteins and lipids whose conformations are critically temperature dependent. METHOD: This paper extends the traditional thermal switch by utilizing purposely designed network topologies of biomolecular interactions to achieve the switching function. By assuming the general Arrhenius law for biochemical reactions, we explore the full space of all three-node genetic interaction networks to screen topologies capable of thermal bioswitches. Three target bioswitches, i.e., thermal-inducible Off–On, cold-inducible On–Off, and hybrid Off–On-Off double switches, are considered separately. CONCLUSIONS: We identify the minimal and core network skeletons that are basic and essential for building robust high-performance bioswitches: three Off–On motifs, three On–Off motifs, and an incoherent feedforward motif for an Off–On-Off double switch. Functional topologies are implicitly preferential in choosing parameter values to achieve the target functions. The scenario of the topology-based bioswitch we propose here is an extension of molecule-based bioswitches and would be valuable in aiding the rational design and synthesis of efficient high-performance thermal bioswitches.