Qian Ruo-Can, Zhou Ze-Rui, Guo Weijie, Wu Yuting, Yang Zhenglin, Lu Yi
Key Laboratory for Advanced Materials, Feringa Nobel Prize Scientist Joint Research Center, Joint International Laboratory for Precision Chemistry, Frontiers Science Center for Materiobiology & Dynamic Chemistry, School of Chemistry and Molecular Engineering, East China University of Science and Technology, Shanghai 200237, P. R. China.
J Am Chem Soc. 2021 Apr 21;143(15):5737-5744. doi: 10.1021/jacs.1c00060. Epub 2021 Mar 22.
Regulating cell-cell interactions and cell behaviors via cell surface engineering is of significance for biological research such as cell fate control and cell therapy. While extensive efforts have been made to induce cell-cell assembly via various cell surface modifications triggered by macromolecules or organic metabolites, controllable cell-cell interactions that include both assembly and disassembly triggered by metal ions remain a challenge. Herein, we report a strategy based on DNAzymes to realize controllable cell-cell interactions, triggered by metal ions. The metal-dependent DNAzyme-based cleavage can effectively manipulate cell behaviors, including cell-cell conjunctions and disaggregation. Using a Zn-specific DNAzyme, a Mg-specific DNAzyme, and their respective substrate strands as the building blocks, the corresponding DNA double-chain switches enabling two-factor disassembly are demonstrated. Moreover, the method has been applied to control the assembly and disassembly between two cell spheroids. Since a wide variety of metal-specific DNAzymes are available, this method can be readily applied to construct cell dynamic systems controlled by other metal ions, providing a smart and versatile platform to regulate dynamic cell behavior.
通过细胞表面工程调控细胞间相互作用和细胞行为对于诸如细胞命运控制和细胞治疗等生物学研究具有重要意义。尽管人们已经做出了广泛努力，通过大分子或有机代谢物引发的各种细胞表面修饰来诱导细胞间组装，但由金属离子触发的包括组装和解离在内的可控细胞间相互作用仍然是一个挑战。在此，我们报告了一种基于脱氧核酶的策略，以实现由金属离子触发的可控细胞间相互作用。基于金属依赖性脱氧核酶的切割可以有效地操纵细胞行为，包括细胞间连接和解聚。使用锌特异性脱氧核酶、镁特异性脱氧核酶及其各自的底物链作为构建模块，展示了能够实现双因素解离的相应DNA双链开关。此外，该方法已应用于控制两个细胞球之间的组装和解离。由于有各种各样的金属特异性脱氧核酶可供使用，该方法可以很容易地应用于构建由其他金属离子控制的细胞动态系统，为调节动态细胞行为提供了一个智能且通用的平台。
