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Cell Membrane Targeting via Spacer Length-Engineered Amphiphilic DNA Frameworks.

Ziwei Zhou1, Jiang Qian1,2, Chengpin Liang3

  • 1State Key Laboratory of Synergistic Chem-Bio Synthesis, School of Chemistry and Chemical Engineering, New Cornerstone Science Laboratory, Frontiers Science Center for Transformative Molecules and National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai 200240, China.

ACS Applied Bio Materials
|April 21, 2026
PubMed
Summary
This summary is machine-generated.

Optimizing DNA nanostructures for cell membrane targeting involves adjusting spacer length. Moderate spacer increases enhance DNA nanostructure membrane binding, improving cellular sensing tools.

Keywords:
amphiphilic DNA frameworkcell membrane targetingspacer lengthstructural flexibilitytetrahedral DNA frameworks

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Area of Science:

  • Biotechnology
  • Nanotechnology
  • Molecular Biology

Background:

  • Cell membrane-anchored DNA nanostructures are crucial for cellular sensing and engineering.
  • Their efficiency is often hindered by mechanical incompatibility between rigid DNA and dynamic cell membranes.

Purpose of the Study:

  • To investigate how structural flexibility, controlled by spacer length, impacts the membrane-targeting efficiency of DNA nanostructures.
  • To optimize DNA nanostructures for enhanced cell membrane interaction.

Main Methods:

  • Systematic insertion of poly(thymine) spacers of varying lengths into amphiphilic tetrahedral DNA frameworks (TDFs).
  • Quantitative fluorescence analysis and live-cell confocal imaging to assess membrane targeting.
  • Time-course analysis to evaluate the dynamics of membrane association.

Main Results:

  • Spacer length significantly influences membrane targeting efficiency; moderate lengths improve performance.
  • TDFs with a 10-thymine spacer showed a ~6-fold increase in membrane targeting signal compared to spacer-free designs.
  • Spacer engineering impacts the rate of membrane targeting, with the 10T construct demonstrating the fastest signal accumulation.

Conclusions:

  • Spacer engineering is a key factor in determining the membrane-targeting capability of DNA nanostructures.
  • This study provides a design strategy to enhance the performance of DNA-based cell membrane probes and tools.