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Cell-Membrane-Anchored Synthetic Dynamic DNA Circuits for Signaling Transient Cell Migration.

Nina Lin1, Yu Ouyang2, Yunlong Qin2

  • 1School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, China.

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|September 12, 2025
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Researchers developed a DNA reaction circuit in MCF-7 cells that dynamically reconfigures into a constitutional dynamic network (CDN). This network transiently forms Met-dimer complexes, activating intracellular signaling and controlling cell migration.

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Area of Science:

  • Biotechnology and Synthetic Biology
  • Molecular and Cellular Biology
  • Nanotechnology

Background:

  • The mesenchymal-epithelial transition (Met) receptor is crucial in cellular signaling and cancer progression.
  • Mimicking natural cell membrane signaling networks with synthetic circuits presents a significant challenge.
  • Constitutional dynamic networks (CDNs) offer a framework for dynamic molecular self-assembly and reconfiguration.

Purpose of the Study:

  • To engineer a DNA reaction circuit within live MCF-7 cells to emulate the Met receptor signaling pathway.
  • To investigate the dynamic reconfiguration of the circuit into a CDN and its effect on Met-dimer formation.
  • To explore the downstream cellular responses, including intracellular signaling and cell motility, triggered by the CDN.

Main Methods:

  • Anchoring a DNA reaction circuit with Met receptor aptamers onto the membrane of MCF-7 cells.
  • Utilizing an auxiliary fuel strand and nicking enzyme to induce dynamic reconfiguration into a CDN.
  • Employing temporal confocal fluorescence microscopy to characterize CDN dynamics and Met-dimer formation.
  • Assessing intracellular signaling pathway activation (Akt/FAK phosphorylation) and cell migration.

Main Results:

  • The DNA reaction circuit successfully reconfigured into a CDN within live MCF-7 cell membranes.
  • Transient formation and depletion of allosterically stabilized Met-dimer complexes were observed.
  • CDN-mediated Met-dimer formation induced Akt/FAK phosphorylation and transiently controlled MCF-7 cell migration.

Conclusions:

  • A synthetic DNA reaction circuit can effectively emulate cell membrane signaling networks and dynamic processes.
  • The engineered CDN enables controlled, transient formation of Met-dimer complexes, modulating cellular behavior.
  • This approach provides a novel platform for studying and manipulating cell signaling and motility.