State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China.
Medical Science and Technology Innovation Center, Shandong First Medical University, Jinan 250117, China.
J Am Chem Soc. 2023 Mar 8;145(9):5092-5104. doi: 10.1021/jacs.2c11150. Epub 2023 Feb 23.
Cell surface engineering provides access to custom-made cell interfaces with desirable properties and functions. However, cell-selective covalent labeling methods that can simultaneously install multiple molecules with different functions are scarce. Herein, we report an aptamer-enabled proximity catalytic covalent labeling platform for multifunctional surface reconfiguration of target cells in mixed cell populations. By conjugating peroxidase with cell-selective aptamers, the probes formed can selectively bind target cells and catalyze target-cell-localized covalent labeling . The universal applicability of the platform to different phenol-modified functional molecules allows us to perform a variety of manipulations on target cells, including labeling, tracking, assembly regulation, and surface remodeling. In particular, the platform has the ability of multiplexed covalent labeling, which can be used to install two mutually orthogonal click reactive molecules simultaneously on the surface of target cells. We thus achieve "multitasking" in complex multicellular systems: programming and tracking specific cell-cell interactions. We further extend the functional molecules to carbohydrates and perform ultrafast neoglycosylation on target living cells. These newly introduced sugars on the cell membrane can be recognized and remodeled by a glycan-modifying enzyme, thus providing a method package for cell-selective engineering of the glycocalyx.
细胞表面工程提供了一种获取具有理想性质和功能的定制化细胞界面的途径。然而，能够同时安装具有不同功能的多种分子的细胞选择性共价标记方法却很稀缺。在此，我们报告了一种适体介导的邻近催化共价标记平台，用于在混合细胞群体中对靶细胞进行多功能表面重构。通过将过氧化物酶与细胞选择性适体偶联，形成的探针可以选择性地结合靶细胞，并催化靶细胞局部的共价标记。该平台对不同酚修饰功能分子的普遍适用性允许我们对靶细胞进行多种操作，包括标记、跟踪、组装调控和表面重塑。特别是，该平台具有多重共价标记的能力，可以同时在靶细胞表面安装两种相互正交的点击反应性分子。因此，我们在复杂的多细胞系统中实现了“多任务处理”：编程和跟踪特定的细胞-细胞相互作用。我们进一步将功能分子扩展到碳水化合物，并在靶活细胞上进行超快的新生糖基化。细胞膜上引入的这些新糖可以被糖基化修饰酶识别和重塑，从而为糖萼的细胞选择性工程提供了一种方法包。
