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<p>Reconstructing cellular complexity is a central challenge in synthetic biology, with profound implications for understanding life and advancing bio-inspired nanotechnologies. A critical step towards this goal is replicating the dynamic interplay among membrane components and their functions. Here we demonstrate a double-necked synthetic cell microreactor (DCM) that incorporates two dynamic, DNA-based pores in the membrane of a giant unilamellar vesicle. The formation of the DCM leverages a signalling pathway mediated by giant unilamellar vesicle membrane dynamics to coordinate interactions between light-responsive small pores and self-arranged sealable large pores. This system enables sequential, on-demand delivery of molecular reactants with high spatiotemporal precision. Using DCMs, we demonstrate confined biochemical reactions, including a glucose oxidase–myoglobin cascade, cytoskeleton-mimetic actin polymerization and bundling, cell-free Spinach RNA transcription and the synthesis of three-dimensional DNA crystals that extend beyond natural systems. By coupling orchestrated multistep signalling with dynamic control of membrane permeability, the DCM establishes a versatile platform for emulating and expanding the functional complexity of natural cellular systems.</p><p></p>

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A synthetic cell microreactor with two types of interacting dynamic DNA-based pores

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月15日

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  • Sisi Fan,
  • Longjiang Ding,
  • Benjamin Renz,
  • Allen P. Liu,
  • Thomas Speck,
  • Hao Yan,
  • Stephan Nussberger,
  • Na Liu

摘要

Reconstructing cellular complexity is a central challenge in synthetic biology, with profound implications for understanding life and advancing bio-inspired nanotechnologies. A critical step towards this goal is replicating the dynamic interplay among membrane components and their functions. Here we demonstrate a double-necked synthetic cell microreactor (DCM) that incorporates two dynamic, DNA-based pores in the membrane of a giant unilamellar vesicle. The formation of the DCM leverages a signalling pathway mediated by giant unilamellar vesicle membrane dynamics to coordinate interactions between light-responsive small pores and self-arranged sealable large pores. This system enables sequential, on-demand delivery of molecular reactants with high spatiotemporal precision. Using DCMs, we demonstrate confined biochemical reactions, including a glucose oxidase–myoglobin cascade, cytoskeleton-mimetic actin polymerization and bundling, cell-free Spinach RNA transcription and the synthesis of three-dimensional DNA crystals that extend beyond natural systems. By coupling orchestrated multistep signalling with dynamic control of membrane permeability, the DCM establishes a versatile platform for emulating and expanding the functional complexity of natural cellular systems.