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<p>The selective capture of endogenous cells and proteins holds immense potential in regenerative medicine, single-cell analysis, biosensing and cell therapy. However, conventional multivalent platforms suffer from uncontrolled ligand distribution and poor spatial alignment, limiting capture efficiency. Here we provide a protocol for a programmable tetrahedral DNA nanostructure (TDN) platform that enables precise spatial control of capture ligands through site-specific editability. This protocol describes two distinct capture systems: (1) an aptamer-functionalized TDN for the selective capture of mesenchymal stem cells, which increases binding affinity 2.25-fold and achieves ~90% capture efficiency, and (2) a peptide-functionalized TDN–hydrogel for sequestering endogenous growth factors, which enhances capture efficiency from &lt;40% with conventional methods to nearly 90%. The complete protocol, from computational design and nanostructure assembly to in vitro functional validation, can be completed in ~10–20 d, with subsequent in vivo studies extending over several weeks. This versatile platform enables the rational design of high-efficiency capture agents for diverse biological targets, providing a powerful and adaptable tool for tissue engineering, cell sorting and biosensing.</p>

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A programmable DNA tetrahedron platform for selective and efficient capture of cells and proteins

  • 期刊论文

  • 发表日期：

    2026年7月27日

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  • Xingyu Chen,
  • Wumeng Yin,
  • Songhang Li,
  • Xiaoxiao Cai,
  • Yunfeng Lin,
  • Taoran Tian

摘要

The selective capture of endogenous cells and proteins holds immense potential in regenerative medicine, single-cell analysis, biosensing and cell therapy. However, conventional multivalent platforms suffer from uncontrolled ligand distribution and poor spatial alignment, limiting capture efficiency. Here we provide a protocol for a programmable tetrahedral DNA nanostructure (TDN) platform that enables precise spatial control of capture ligands through site-specific editability. This protocol describes two distinct capture systems: (1) an aptamer-functionalized TDN for the selective capture of mesenchymal stem cells, which increases binding affinity 2.25-fold and achieves ~90% capture efficiency, and (2) a peptide-functionalized TDN–hydrogel for sequestering endogenous growth factors, which enhances capture efficiency from <40% with conventional methods to nearly 90%. The complete protocol, from computational design and nanostructure assembly to in vitro functional validation, can be completed in ~10–20 d, with subsequent in vivo studies extending over several weeks. This versatile platform enables the rational design of high-efficiency capture agents for diverse biological targets, providing a powerful and adaptable tool for tissue engineering, cell sorting and biosensing.