[论文解读] Inverse design of a pyrochlore lattice of DNA origami through model-driven experiments

Hao Liu, Michael Matthies+11 more|arXiv (Cornell University)|Oct 17, 2023

Advanced biosensing and bioanalysis techniquesBiochemistry, Genetics and Molecular Biology参考文献 44被引用 3

一句话总结

本文提出了一种模型驱动的逆向设计流程，结合SAT-assembly优化与粗粒度模拟，实现了使用DNA折纸术在实验上验证的钙钛矿晶格自组装。通过迭代排除动力学陷阱和竞争相，该方法实现了高产率、无陷阱的三维目标晶格自组装，经SAXS和SEM验证，八面体和二十面体设计的晶格参数分别为156.4 nm和159.1 nm。

ABSTRACT

Sophisticated statistical mechanics approaches and human intuition have demonstrated the possibility to self-assemble complex lattices or finite size constructs, but have mostly only been successful in silico. The proposed strategies quite often fail in experiment due to unpredicted traps associated to kinetic slowing down (gelation, glass transition), as well as to competing ordered structures. An additional challenge that theoretical predictions face is the difficulty to encode the desired inter-particle interaction potential with the currently available library of nano- and micron-sized particles. To overcome these issues, we conjugate here SAT-assembly -- a patchy-particle interaction design algorithm based on constrained optimization solvers -- with coarse-grained simulations of DNA nanotechnology to experimentally realize trap-free self-assembly pathways. As a proof of concept we investigate the assembly of the pyrochlore (also known as tetrastack) lattice, a highly coveted 3D crystal lattice due to its promise in construction of optical metamaterials. We confirm the successful assembly with two different patchy DNA origami designs via SAXS as well as SEM visualization of the silica-coated lattice. Our approach offers a versatile modeling pipeline that starts from patchy particles designed in silico and ends with wireframe DNA origami that self-assemble into the desired structure.

研究动机与目标

• 为克服通常阻碍复杂自组装纳米结构实验实现的动力学陷阱和竞争相。
• 开发一种可推广的设计框架，弥合理论预测与DNA纳米技术实验成功之间的差距。
• 实现实验上实现高度期待的钙钛矿晶格，该结构在光学超材料中具有广阔前景。
• 创建一种可扩展的、开源的流程，用于设计基于patchy粒子相互作用的长程和有限尺寸组装。
• 证明通过计算优化、模拟与针对性实验的协同作用，可实现复杂的晶格几何结构。

提出的方法

• 使用SAT-assembly算法通过将晶格拓扑转换为布尔子句，并求解满足晶胞约束的相互作用矩阵，来设计patchy粒子相互作用。
• 在一系列温度下进行粗粒度分子动力学模拟，以识别并筛选出动力学陷阱和竞争相。
• 在后续的SAT求解器迭代中显式禁止不良状态，从而优化相互作用设计，仅促进目标钙钛矿晶格的形成。
• 最终的patchy粒子设计通过特定DNA序列和连接点在DNA折纸术中实现，以编码方向性相互作用。
• 通过小角X射线散射（SAXS）和扫描电子显微镜（SEM）进行实验验证，包括聚焦离子束（FIB）横截面分析以研究内部结构。
• 在核苷酸级别的粗粒度模型中验证了设计的patchy相互作用与DNA纳米结构实现之间的兼容性。

Figure 1: Workflow of the computational design with SAT-assembly: a) The topology of the unit cell of a pyrochlore lattice, where each particle has six neighbors. b) The design problem to find a fixed number of species of patchy particles that satisfy the unit cell lattice is translated into a set o

实验结果

研究问题

• RQ1 基于约束优化和模拟的计算设计流程是否能成功引导复杂三维晶格（如钙钛矿结构）的实验自组装？
• RQ2 在patchy粒子相互作用的逆向设计过程中，如何系统性地识别并消除动力学陷阱和竞争有序相？
• RQ3 该设计流程在多大程度上可推广至其他复杂晶格或有限尺寸组装，而不仅限于钙钛矿晶格？
• RQ4 DNA折纸术能否被工程化以实现所需的patchy粒子相互作用，从而在三维空间中实现长程有序？
• RQ5 哪些实验技术能够可靠地确认在介观尺度上形成钙钛矿晶格，包括晶格参数和内部有序性？

主要发现

• 逆向设计流程成功消除了动力学陷阱和竞争相，形成仅生成目标钙钛矿晶格的自组装路径。
• SAXS测量证实了晶格结构，八面体DNA折纸术设计的晶格参数为156.4 nm，二十面体设计为159.1 nm。
• SEM和FIB横截面成像显示长程内部有序性，无明显缺陷，证实了组装晶格的结构保真度。
• 通过两种不同的DNA折纸术设计实现了实验实现，证明了该设计流程的鲁棒性和通用性。
• 该方法可通过DNA折纸术构建块的尺寸和内部特征精确控制晶格参数，从而影响晶格的最终光学性能。
• 整个设计与模拟流程作为开源软件发布，可广泛应用于其他复杂纳米结构。

Figure 2: Transferring the patchy particle design to the sequence design of DNA nanostructures with oxDNA simulations of the assembled lattice. a Octahedral and c icosahedral DNA origamis are selected for the experimental implementation of patchy particles, with patches realized as single-stranded o