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Synthesis of an Intein-mediated Artificial Protein Hydrogel
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DNA Framework Nucleator-Enabled Intelligent Hydrogel Interfaces on Living Cells.

Yuxuan Wu1, Yuanhao Wang1, Jingrui Yang1

  • 1Department of Liver Surgery, School of Medicine, Shanghai Institute of Transplantation, Renji Hospital, Shanghai Jiao Tong University, Shanghai, China.

Small (Weinheim an Der Bergstrasse, Germany)
|May 30, 2026
PubMed
Summary
This summary is machine-generated.

Researchers engineered intelligent hydrogel interfaces on cell surfaces using DNA framework nucleators for precise cellular control. This novel approach enhances stimuli-responsive functions and enables complex logic gate operations for advanced cell-based applications.

Keywords:
DNA hydrogelDNA nanotechnologycell membrane engineeringhybridization chain reactiontetrahedral DNA framework

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Area of Science:

  • Biotechnology
  • Synthetic Biology
  • Materials Science

Background:

  • Precise cellular manipulation requires engineering intelligent interfaces on living cells.
  • Current methods for creating cellular interfaces often lack fidelity and dynamic regulation.

Purpose of the Study:

  • To develop a DNA framework nucleator (DFN)-guided strategy for controlled assembly of high-fidelity stimuli-responsive intelligent hydrogel interfaces (HIs) on living cell surfaces.
  • To investigate the performance of DFN-guided HIs in terms of response efficiency and logic gate function.

Main Methods:

  • Utilized a rigid tetrahedral DNA framework as the structural core for DFNs, acting as nucleation sites on the cell membrane.
  • Directed localized branched hybridization chain reaction for single-cell HI formation.
  • Integrated dual-locked, crosstalk-free logic gate functions for specific molecular triggers (ATP and microRNA-122).

Main Results:

  • Achieved a response efficiency of ~90.7% for ATP-responsive HIs, a ~2.9-fold enhancement over flexible DNA nucleators.
  • Demonstrated a high-fidelity AND-gate function with ~98.5% response efficiency and <4.0% background crosstalk for dual triggers (ATP and microRNA-122), outperforming controls by 4.2-fold.
  • Showcased the importance of ordered nucleation for high-fidelity signal processing at cellular interfaces.

Conclusions:

  • DFN-guided strategy enables the controlled assembly of high-fidelity, stimuli-responsive intelligent hydrogel interfaces on living cells.
  • The platform supports advanced logic gate functions, moving beyond static encapsulation to dynamic, regulated cellular systems.
  • Established a versatile platform for next-generation programmable cell-based applications requiring precise cellular control and signal processing.