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Proximity-Induced Phosphatase-Recruiting DNA Feedback Switch for Self-Adaptive Modulation of Receptor Signaling and

Yuchen Wu1, Guanyu Yin1, Qin Zhang1

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Scientists created a DNA feedback switch that controls cell signaling by sensing receptor proximity. This bioinspired nanomedicine platform precisely regulates cell behavior and offers potential for adaptive therapies.

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Area of Science:

  • Biotechnology
  • Nanomedicine
  • Molecular Biology

Background:

  • Transmembrane receptors are crucial for cell signaling, tissue homeostasis, and disease.
  • Current methods struggle to control cellular processes based on spatial cues like molecular proximity.
  • Dysregulated receptor signaling contributes to disease initiation and progression.

Purpose of the Study:

  • To develop a novel system for precise and self-adaptive modulation of transmembrane receptor signaling.
  • To emulate natural receptor feedback regulation using a proximity-induced mechanism.
  • To create a bioinspired nanomedicine platform for controlling cellular processes.

Main Methods:

  • Developed a proximity-induced phosphatase-recruiting DNA feedback switch (PPDFS).
  • Utilized DNA nanostructures and aptamer-mediated molecular recognition for sensor design.
  • Engineered PPDFS to detect receptor dimerization and recruit the phosphatase PTPRF.

Main Results:

  • PPDFS sensitively detects cell surface receptor dimerization.
  • Receptor proximity triggers both signaling activation and PPDFS-mediated inhibition, maintaining homeostasis.
  • Demonstrated PPDFS regulation of epithelial-mesenchymal transition (EMT), cytoskeletal changes, and cell migration.

Conclusions:

  • PPDFS provides specific and self-adaptive control over transmembrane receptor signaling.
  • The system elucidates the signaling cascade from receptor activity to cellular responses like EMT.
  • PPDFS represents a versatile nanomedicine platform adaptable to various receptor systems for precise therapeutic control.