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

Honglu Zhang, Yu Wang, Huan Zhang, Xiaoguo Liu, Antony Lee, Qiuling Huang, Fei Wang, Jie Chao, Huajie Liu, Jiang Li, Jiye Shi, Xiaolei Zuo, Lihua Wang, Lianhui Wang, Xiaoyu Cao, Carlos Bustamante, Zhongqun Tian () and Chunhai Fan ()
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Honglu Zhang: Chinese Academy of Sciences
Yu Wang: Xiamen University
Huan Zhang: Chinese Academy of Sciences
Xiaoguo Liu: Shanghai Jiao Tong University
Antony Lee: University of California
Qiuling Huang: Chinese Academy of Sciences
Fei Wang: Shanghai Jiao Tong University
Jie Chao: Nanjing University of Posts and Telecommunications (NUPT)
Huajie Liu: Chinese Academy of Sciences
Jiang Li: Chinese Academy of Sciences
Jiye Shi: Chinese Academy of Sciences
Xiaolei Zuo: Shanghai Jiao Tong University
Lihua Wang: Chinese Academy of Sciences
Lianhui Wang: Nanjing University of Posts and Telecommunications (NUPT)
Xiaoyu Cao: Xiamen University
Carlos Bustamante: University of California
Zhongqun Tian: Xiamen University
Chunhai Fan: Chinese Academy of Sciences

Nature Communications, 2019, vol. 10, issue 1, 1-11

Abstract: Abstract 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.

Date: 2019
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DOI: 10.1038/s41467-019-09004-4

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