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<p>Self-assembly of nanoscale building blocks with programmable geometries and interactions offers a powerful route to engineer materials that mimic the complexity of biological structures. DNA origami provides an exceptional platform for this purpose, enabling precise control over subunit shape, binding angles, and interaction specificity. Here we present a modular DNA origami design approach to address the challenges of assembling geometrically complex nanoscale structures, including those with nonuniform curvatures. This approach features a core structure that completely conserves the scaffold routing across different designs and preserves more than 70% of the DNA staples between designs, dramatically reducing both cost and effort, while enabling precise and independent programming of subunit interactions and binding angles through adjustable overhang lengths and sequences. Using cryogenic electron microscopy, gel electrophoresis, and coarse-grained simulations, we validate a set of robust design rules and demonstrate the assembly of diverse self-limiting structures, including anisotropic shells, a <i>T</i>&#xa0;=&#xa0;13 icosahedral shell, and a toroid with globally varying curvature. This modular strategy provides an efficient and cost-effective framework for the synthetic fabrication of complex nanostructures.</p>

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Modular programming of interaction and geometric specificity enables assembly of complex DNA origami nanostructures

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年12月11日

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  • Rupam Saha,
  • Daichi Hayakawa,
  • Thomas E. Videbæk,
  • Mason Price,
  • Wei-Shao Wei,
  • Juanita Pombo,
  • Daniel Duke,
  • Gaurav Arya,
  • Gregory M. Grason,
  • W. Benjamin Rogers,
  • Seth Fraden

摘要

Self-assembly of nanoscale building blocks with programmable geometries and interactions offers a powerful route to engineer materials that mimic the complexity of biological structures. DNA origami provides an exceptional platform for this purpose, enabling precise control over subunit shape, binding angles, and interaction specificity. Here we present a modular DNA origami design approach to address the challenges of assembling geometrically complex nanoscale structures, including those with nonuniform curvatures. This approach features a core structure that completely conserves the scaffold routing across different designs and preserves more than 70% of the DNA staples between designs, dramatically reducing both cost and effort, while enabling precise and independent programming of subunit interactions and binding angles through adjustable overhang lengths and sequences. Using cryogenic electron microscopy, gel electrophoresis, and coarse-grained simulations, we validate a set of robust design rules and demonstrate the assembly of diverse self-limiting structures, including anisotropic shells, a T = 13 icosahedral shell, and a toroid with globally varying curvature. This modular strategy provides an efficient and cost-effective framework for the synthetic fabrication of complex nanostructures.