南京邮电大学晁洁团队——环状支架模块化组装,构建可编程高阶 DNA 纳米管

📚研究背景

自然界中，生物系统通过纳米尺度生物分子的模块化组装实现复杂功能，如肌球蛋白的分段结构、病毒衣壳的重复亚基组装，均具备结构稳定、逻辑可控、功能可定制的特点，为人工纳米系统设计提供了核心灵感。

合成生物学领域，DNA 凭借碱基互补配对的可编程性、结构稳定性，成为构建人工模块化系统的核心材料，其中DNA 瓦片与DNA 折纸是两大主流策略：

综上，现有策略难以平衡产率、稳定性、完整性、可扩展性四大核心性能，如何整合二者优势、开发新型组装策略，成为突破高阶 DNA 纳米结构构建瓶颈的关键问题。

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FIGURE 1. (a) Schematic diagrams of the modular assembly process of DNA tile, DNA origami, and DNA-nanotube tile. (b) Core performance of the three strategies was quantitatively compared through radar diagrams, with the evaluation dimensions covering modular, yield (overall yield of finite-sized high-order structures), stability, integrity, and scalability. (c) Schematic diagrams of the technical process and functional application of the DNT.

1. DNA 环状支架与 DNT 瓦片的构建及表征

Figure 2. Assembly of DNA-nanotube tiles using DNA annular scaffolds.

Figure 3. Schematic diagram and AFM images of DNT polymer structures and Y-shaped and cross-shaped superstructures. (a) Schematic diagram and AFM images of DNT polymer structures. The molecular weight of DNT polymers increases from left to right and from top to bottom. (b) Schematic diagram and AFM images of DNT Y-shaped and cross-shaped superstructures. Scale bars: 50 nm.

2. DNT 瓦片的模块化高阶组装

3. 基于 DNT 的动态逻辑门与电路构建

Figure 5. (a) DNT-based Boolean logic gates. (b) Schematic diagram of an AND gate based on DNT homodimers and its corresponding truth table; representative AFM images of the DNT-based AND gate responding to different inputs. (c) Schematic diagram of a NOR gate based on DNT heterotrimers and its corresponding truth table; representative AFM images of the DNT-based NOR gate responding to different inputs.

Scale bars: 50 nm.

Figure 6. DNT-based modular circuit structure. (a) Modular circuit structure based on the DNT with a MAJORITY function and a schematic diagram corresponding to the MAJORITY function. (b) Representative AFM images (from top to bottom: no input, In 1 + In 2, In 1 + In 2 + In 3). (c) Fluorescence output response of the MAJORITY circuit to different inputs. Dotted lines indicate the decision thresholds for the output.

本研究开创性提出DNA 环状支架辅助模块化组装策略，成功攻克现有 DNA 纳米技术产率低、稳定性差、可扩展性受限的核心痛点，实现三大关键突破：

1. 结构层面：以分散式环状支架构建 DNT 瓦片，兼顾超 99% 高组装产率、优异结构稳定性、精准尺寸可控性，完美融合 DNA 瓦片与 DNA 折纸的双重优势；
2. 组装层面：实现从线性寡聚物到复杂超结构的模块化、可编程、可预测组装，大幅拓展 DNA 纳米结构设计空间；
3. 功能层面：构建动态可重构 DNA 逻辑门与电路，实现纳米尺度分子计算，为 DNA 纳米技术从静态结构向动态功能器件转化提供新思路。

综上，该策略为安全高效、可规模化制备的高阶 DNA 纳米结构提供了通用框架，在生物传感、药物递送、分子计算、纳米器件等领域具备极高转化潜力，为下一代智能生物纳米材料研发奠定坚实基础。