Direct visualization of pathways followed by single molecules while they spontaneously self-assemble into supramolecular biological machines may provide fundamental knowledge to guide molecular therapeutics and the bottom-up design of nanomaterials and nanodevices. Here, high-speed atomic force microscopy is used to visualize self-assembly of the bidimensional lattice of protein molecules that constitutes the framework of the mature human immunodeficiency virus capsid. By real-time imaging of the assembly reaction, individual transient intermediates and reaction pathways followed by single molecules could be revealed. As when assembling a jigsaw puzzle, the capsid protein lattice is randomly built. Lattice patches grow independently from separate nucleation events whereby individual molecules follow different paths. Protein subunits can be added individually, while others form oligomers before joining a lattice or are occasionally removed from the latter. Direct real-time imaging of supramolecular self-assembly has revealed a complex, chaotic process involving multiple routes followed by individual molecules that are inaccessible to bulk (averaging) techniques.

中文翻译：

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通过随机途径构建病毒衣壳蛋白格子的单分子的可视化。

当单个分子自发地自组装成超分子生物机器时，路径的直接可视化可能为指导分子治疗以及纳米材料和纳米装置的自下而上设计提供基础知识。在这里，高速原子力显微镜用于可视化构成成熟人免疫缺陷病毒衣壳框架的蛋白质分子二维晶格的自组装。通过对组装反应的实时成像，可以揭示单个瞬态中间体和反应路径以及单个分子。与组装拼图游戏一样，衣壳蛋白晶格是随机构建的。晶格斑块独立于独立的成核事件而生长，由此单个分子遵循不同的路径。蛋白质亚基可以单独添加，而其他亚基在连接晶格之前会形成寡聚体，有时会从中除去。超分子自组装的直接实时成像显示了一个复杂的，混乱的过程，涉及多个路径，随后是单个分子，而批量（平均）技术无法访问这些分子。