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

H Zhang, Y Wang, H Zhang, X Liu, A Lee… - Nature …, 2019 - nature.com
H Zhang, Y Wang, H Zhang, X Liu, A Lee, Q Huang, F Wang, J Chao, H Liu, J Li, J Shi, X Zuo…
Nature Communications, 2019nature.com
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 …
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.
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