Continuously tunable multistability in DNA replication networks

Multistable systems, ideally, could stabilize at any desired, switchable state within a continuous spectrum. However, conventional systems, constrained by signal-mediated mutual activation or inhibition, are limited to a finite set of discrete steady states. Here, we propose a rational framework for achieving continuously tunable multistability through reversible displacement reaction-mediated competition between positive autoregulatory DNA polymerization/nicking modules. This framework harnesses the chemical energy of dNTP hydrolysis to suppress spontaneous interconversion between modules for stabilizing at any target state along a continuous compositional gradient. With unparalleled tunability, the framework enables continuous, orthogonal state transitions and concentration-adaptive molecular memory in response to transient stimuli. Moreover, the single-stranded DNAs generated by polymerization/nicking reactions can be customized with predefined structures and functions, enabling continuously multistable control over downstream processes, e.g., biocatalysis and RNA transcription, while maintaining multistability. This framework establishes a versatile and robust platform for developing chemical and material systems with continuously tunable multistability. Multistable systems, ideally, could stabilize at any desired, switchable state within a continuous spectrum, however, conventional systems are limited to a finite set of discrete steady states. Here, the authors propose a rational framework for achieving continuously tunable multistability through reversible displacement reaction-mediated competition between positive autoregulatory DNA polymerization/nicking modules.