Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
ACS Nano. 2022 Apr 26;16(4):6666-6675. doi: 10.1021/acsnano.2c01178. Epub 2022 Apr 11.
DNA-based nanoparticle assemblies have emerged as leading candidates in the development of bioimaging materials, photonic devices, and computing materials. Here, we combine atomistic simulations and experiments to characterize the wrapping mechanism of chimeric single-stranded DNA (ssDNA) on CdSe-ZnS (core-shell) quantum dots (QDs) at different ratios of the phosphorothioate (PS) modification of the bases. We use an implicit solvent, all-atom ssDNA model to match the experimentally calculated ssDNA conformation at low salt concentrations. Through simulation, we find that 3-mercaptopropionic acid (MPA) induces electrostatic repulsion and O-(2-mercaptoethyl)-Ó-methyl-hexa (ethylene glycol) (mPEG) induces steric exclusion, and both reduce the binding affinity of ssDNA. In both simulation and experiment, we find that ssDNA is closer to the QD surface when the QD size is larger. The effect of the PS-base ratio on the conformation of ssDNA is also elaborated in this work. We found through MD simulations, and confirmed by transmission electron microscopy, that the maximum valence numbers are 1, 2, and 3 on QDs of 6, 9, and 14 nm in diameter, respectively. We conclude that the maximum ssDNA valence number is linearly related to the QD size, ∝ , and justify this finding through an electrostatic repulsion mechanism.
基于 DNA 的纳米粒子组装体已成为生物成像材料、光子器件和计算材料发展的主要候选者。在这里，我们结合原子模拟和实验来研究在不同碱基磷硫酰化（PS）修饰比例下，嵌合单链 DNA（ssDNA）在 CdSe-ZnS（核壳）量子点（QD）上的包裹机制。我们使用隐溶剂、全原子 ssDNA 模型来匹配在低盐浓度下实验计算出的 ssDNA 构象。通过模拟，我们发现 3-巯基丙酸（MPA）诱导静电排斥，O-(2-巯基乙基)-O-甲基-六（乙二醇）（mPEG）诱导空间排斥，这两种作用都降低了 ssDNA 的结合亲和力。在模拟和实验中，我们都发现当 QD 尺寸较大时，ssDNA 更接近 QD 表面。本工作还详细阐述了 PS-碱基比对 ssDNA 构象的影响。我们通过 MD 模拟发现，并且通过透射电子显微镜证实，在直径为 6、9 和 14nm 的 QD 上，ssDNA 的最大价数分别为 1、2 和 3。我们得出结论，ssDNA 的最大价数与 QD 尺寸呈线性关系，∝，并通过静电排斥机制证明了这一发现。
