Continuously tunable multistability in DNA replication networks
Zhong Rui, Fu Yanjie, Jiang Shubao, Wang Shan, Yue Liang, Tan Weihong
Journal:Nature Communications
IF:18.1
DOI:10.1038/s41467-026-68488-z
PMID:41644952
Published:2026-02-05
research field:合成生物学分子电路设计非平衡生化系统核酸化学系统生物学生物化学
Abstract
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.
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