School of Chemistry and Chemical Engineering, New Cornerstone Science Laboratory, Frontiers Science Center for Transformative Molecules, Zhangjiang Institute for Advanced Study and National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai 200240, China.
Zhangjiang Laboratory, Shanghai 201210, China.
J Am Chem Soc. 2024 Feb 28;146(8):5461-5469. doi: 10.1021/jacs.3c13180. Epub 2024 Feb 14.
Two-dimensional (2D) DNA origami assembly represents a powerful approach to the programmable design and construction of advanced 2D materials. Within the context of hybridization-mediated 2D DNA origami assembly, DNA spacers play a pivotal role as essential connectors between sticky-end regions and DNA origami units. Here, we demonstrated that programming the spacer length, which determines the binding radius of DNA origami units, could effectively tune sticky-end hybridization reactions to produce distinct 2D DNA origami arrays. Using DNA-PAINT super-resolution imaging, we unveiled the significant impact of spacer length on the hybridization efficiency of sticky ends for assembling square DNA origami (SDO) units. We also found that the assembly efficiency and pattern diversity of 2D DNA origami assemblies were critically dependent on the spacer length. Remarkably, we realized a near-unity yield of ∼98% for the assembly of SDO trimers and tetramers via this spacer-programmed strategy. At last, we revealed that spacer lengths and thermodynamic fluctuations of SDO are positively correlated, using molecular dynamics simulations. Our study thus paves the way for the precision assembly of DNA nanostructures toward higher complexity.
二维 (2D) DNA 折纸组装代表了一种强大的可编程设计和构建先进 2D 材料的方法。在杂交介导的 2D DNA 折纸组装的背景下，DNA 间隔物作为粘性末端区域和 DNA 折纸单元之间的关键连接物起着至关重要的作用。在这里，我们证明了通过编程间隔物长度（决定 DNA 折纸单元的结合半径），可以有效地调节粘性末端杂交反应，从而产生不同的 2D DNA 折纸阵列。使用 DNA-PAINT 超分辨率成像，我们揭示了间隔物长度对组装正方形 DNA 折纸 (SDO) 单元的粘性末端杂交效率的显著影响。我们还发现，2D DNA 折纸组装的组装效率和图案多样性严重依赖于间隔物长度。值得注意的是，我们通过这种间隔物编程策略实现了 SDO 三聚体和四聚体组装的近 100%的高产率（约为 98%）。最后，我们通过分子动力学模拟揭示了 SDO 的间隔物长度和热力学波动呈正相关。因此，我们的研究为 DNA 纳米结构的高精度组装朝着更高的复杂性铺平了道路。
