State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Hunan Provincial Key Laboratory of Biomacromolecular Chemical Biology, Hunan University, Changsha, 410082, P. R. China.
School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, 518107, P. R. China.
Angew Chem Int Ed Engl. 2021 Dec 6;60(50):26087-26095. doi: 10.1002/anie.202108210. Epub 2021 Nov 5.
Synthetic molecular robots can execute sophisticated molecular tasks at nanometer resolution. However, a molecular robot capable of controlling cellular behavior remains unexplored. Herein, we report a self-propelled DNA robot operating on the cell membrane to control the migration of a cell. Driven by DNAzyme catalytic activity, the DNA robot could autonomously and stepwise move on the membrane-floating cell-surface receptors in a stochastic manner and simultaneously trigger the receptor-dimerization to activate downstream signaling for cell motility. The cell membrane-associated continuous motion and operation of a DNA robot allowed for the ultrasensitive regulation of MET/AKT signaling and cytoskeleton remodeling to enhance cell migration. Finally, we designed distinct conditional DNA robots to orthogonally manipulate the cell migration in a coculture of mixed cell populations. We have developed a novel strategy to engineer a cell-driving molecular robot, representing a promising avenue for precise cell manipulation with nanoscale resolution.
合成分子机器人可以在纳米分辨率下执行复杂的分子任务。然而，能够控制细胞行为的分子机器人仍未被探索。在此，我们报告了一种在细胞膜上运行的自主式 DNA 机器人，用于控制细胞的迁移。在 DNA 酶催化活性的驱动下，DNA 机器人可以在随机的方式下在膜浮动细胞表面受体上自主且逐步移动，同时触发受体二聚化以激活下游信号转导，从而促进细胞运动。与细胞膜相关的 DNA 机器人的连续运动和操作使得 MET/AKT 信号和细胞骨架重构的超敏调节得以增强细胞迁移。最后，我们设计了不同的条件性 DNA 机器人，以在混合细胞群体的共培养中正交地操纵细胞迁移。我们已经开发出一种新的策略来设计驱动细胞的分子机器人，这代表了一种具有纳米级分辨率的精确细胞操纵的有前途的途径。
