Programming chain-growth copolymerization of DNA hairpin tiles for in-vitro hierarchical supramolecular organization

• Published in: Nature communications 2019-03, Vol.10 (1), p.1006-11, Article 1006
• Main Authors: Zhang, Honglu, Wang, Yu, Zhang, Huan, Liu, Xiaoguo, Lee, Antony, Huang, Qiuling, Wang, Fei, Chao, Jie, Liu, Huajie, Li, Jiang, Shi, Jiye, Zuo, Xiaolei, Wang, Lihua, Wang, Lianhui, Cao, Xiaoyu, Bustamante, Carlos, Tian, Zhongqun, Fan, Chunhai
• Format: Article
• Language: English
• Subjects: 147/3; 639/638/541/960; 639/925/926/1049; A549 Cells; Base Sequence; Catalysis; Catalytic Domain; Copolymerization; Deoxyribonucleic acid; DNA; DNA - chemistry; DNA, Single-Stranded - chemistry; Endocytosis; Filaments; Humanities and Social Sciences; Humans; Hydrogen Bonding; Hydrogen bonds; Mammalian cells; Migration; Models, Genetic; Monomers; multidisciplinary; Nanostructures; Nucleic Acid Conformation; Nucleic Acid Hybridization; Polymerization; Proteins; Science; Science (multidisciplinary); Stiffness; Structure-function relationships; Substrates; Tiles
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-09004-4

Formation of biological filaments via intracellular supramolecular polymerization of proteins or protein/nucleic acid complexes is under programmable and spatiotemporal control to maintain cellular and genomic integrity. Here we devise a bioinspired, catassembly-like isothermal chain-growth approach to copolymerize DNA hairpin tiles (DHTs) into nanofilaments with desirable composition, chain length and function. By designing metastable DNA hairpins with shape-defining intramolecular hydrogen bonds, we generate two types of DHT monomers for copolymerization with high cooperativity and low dispersity indexes. Quantitative single-molecule dissection methods reveal that catalytic opening of a DHT motif harbouring a toehold triggers successive branch migration, which autonomously propagates to form copolymers with alternate tile units. We find that these shape-defined supramolecular nanostructures become substrates for efficient endocytosis by living mammalian cells in a stiffness-dependent manner. Hence, this catassembly-like in-vitro reconstruction approach provides clues for understanding structure-function relationship of biological filaments under physiological and pathological conditions. Formation of biological filaments via intracellular supramolecular polymerization of proteins occurs under programmable and spatiotemporal control to maintain integrity. Here the authors devise a bioinspired isothermal chain-growth approach to programmably copolymerize DNA hairpin tiles into 1D nanofilaments.