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<p>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.</p>

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Continuously tunable multistability in DNA replication networks

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年2月5日

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  • Rui Zhong,
  • Yanjie Fu,
  • Shubao Jiang,
  • Shan Wang,
  • Liang Yue,
  • Weihong Tan

摘要

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.