Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, 02115, USA.
Department of Systems Biology, Harvard Medical School, Boston, MA, 02115, USA.
Nat Commun. 2024 Apr 17;15(1):3293. doi: 10.1038/s41467-024-46978-2.
DNA-based artificial motors have allowed the recapitulation of biological functions and the creation of new features. Here, we present a molecular robotic system that surveys molecular environments and reports spatial information in an autonomous and repeated manner. A group of molecular agents, termed 'crawlers', roam around and copy information from DNA-labeled targets, generating records that reflect their trajectories. Based on a mechanism that allows random crawling, we show that our system is capable of counting the number of subunits in example molecular complexes. Our system can also detect multivalent proximities by generating concatenated records from multiple local interactions. We demonstrate this capability by distinguishing colocalization patterns of three proteins inside fixed cells under different conditions. These mechanisms for examining molecular landscapes may serve as a basis towards creating large-scale detailed molecular interaction maps inside the cell with nanoscale resolution.
基于 DNA 的人工马达使人们能够重现生物功能并创造新的特征。在这里，我们提出了一种分子机器人系统，该系统能够自主且重复地探测分子环境并报告空间信息。一组分子试剂，称为“爬行器”，在周围漫游并从 DNA 标记的靶标复制信息，生成反映其轨迹的记录。基于允许随机爬行的机制，我们表明我们的系统能够计算示例分子复合物中亚基的数量。我们的系统还可以通过从多个局部相互作用生成串联记录来检测多价邻近性。我们通过在不同条件下区分固定细胞内三种蛋白质的共定位模式来证明这种能力。这些用于检查分子景观的机制可能为在细胞内以纳米级分辨率创建具有大规模详细分子相互作用图奠定基础。
