Altering DNA-Programmable Colloidal Crystallization Paths by Modulating Particle Repulsion

Colloidal crystal engineering with DNA can be used to realize precise control over nanoparticle (NP) arrangement. Here, we investigate a case of DNA-based assembly where the properties of DNA as a polyelectrolyte brush are employed to alter a hybridization-driven NP crystallization pathway. Using the coassembly of DNA-conjugated proteins and spherical gold nanoparticles (AuNPs) as a model system, we explore how steric repulsion between noncomplementary, neighboring NPs due to overlapping DNA shells can influence their ligand-directed behavior. Specifically, our experimental data coupled with coarse-grained molecular dynamics (MD) simulations reveal that, by changing factors related to NP repulsion, two structurally distinct outcomes can be achieved. When steric repulsion between DNA−AuNPs is significantly greater than that between DNA–proteins, a lower packing density crystal lattice is favored over the structure that is predicted by design rules based on DNA hybridization considerations alone. This is enabled by the large difference in DNA density on AuNPs versus proteins and can be tuned by modulating the flexibility, and thus conformational entropy, of the DNA on the constituent particles. At intermediate ligand flexibility, the crystallization pathways are energetically similar, and the structural outcome can be adjusted using the density of DNA duplexes on DNA−AuNPs and by screening the Coulomb potential between them. Such lattices are shown to undergo dynamic reorganization upon changing the salt concentration. These data help elucidate the structural considerations necessary for understanding repulsive forces in DNA-mediated assembly and lay the groundwork for using them to increase architectural diversity in engineering colloidal crystals.基于脱氧核糖核酸（DNA）的胶体晶体工程可实现对纳米颗粒（nanoparticle, NP）排布的精准调控。本研究聚焦一类基于DNA的组装体系，利用作为聚电解质刷（polyelectrolyte brush）的DNA的特性，改变杂交驱动的纳米颗粒结晶路径。我们以DNA偶联蛋白与球形金纳米颗粒（spherical gold nanoparticle, AuNP）的共组装为模型体系，探究非互补的相邻纳米颗粒间因DNA壳层重叠产生的空间位阻排斥如何影响其配体导向的组装行为。具体而言，结合实验数据与粗粒度分子动力学（molecular dynamics, MD）模拟结果，本研究发现：通过调控与纳米颗粒排斥作用相关的参数，可获得两种结构截然不同的组装结果。当DNA修饰金纳米颗粒间的空间位阻显著大于DNA修饰蛋白间的位阻时，相较于仅基于DNA杂交设计规则预测的组装结构，低堆积密度的晶格更占优势。该现象源于金纳米颗粒与蛋白表面DNA密度的显著差异，且可通过调节组成颗粒上DNA的柔性（即构象熵）进行调控。当配体柔性处于中间水平时，两条结晶路径的能量相近，此时可通过调整DNA偶联金纳米颗粒表面DNA双链的密度，以及屏蔽颗粒间的库仑势来调控最终的晶格结构。研究发现，此类晶格会在盐浓度改变时发生动态重组。本研究阐明了理解DNA介导组装中排斥力所需的结构考量，为利用此类作用力丰富胶体晶体工程的结构多样性奠定了理论基础。