通过 DNA 发夹嵌段的程序化链式增长共聚反应，实现体外分级超分子组装。
Programming chain-growth copolymerization of DNA hairpin tiles for in-vitro hierarchical supramolecular organization.
机构信息
Division of Physical Biology and Bioimaging Center, Shanghai Synchrotron Radiation Facility, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, 201800, Shanghai, China.
Department of Chemistry, Institute for Quantitative Biosciences (QB3), Department of Physics, Department of Molecular and Cell Biology, Kavli Energy Nanosciences Institute at Berkeley, Howard Hughes Medical Institute, University of California, Berkeley, CA, 94720, USA.
出版信息
Nat Commun. 2019 Mar 1;10(1):1006. 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.
生物纤维的形成是通过蛋白质或蛋白/核酸复合物的细胞内超分子聚合来实现的，这种聚合受到可编程和时空控制，以维持细胞和基因组的完整性。在这里，我们设计了一种受生物启发的、类似于 catassembly 的等温链式生长方法，将 DNA 发夹基元（DHTs）共聚成具有理想组成、链长和功能的纳米纤维。通过设计具有形状定义的分子内氢键的亚稳态 DNA 发夹，我们生成了两种类型的 DHT 单体，用于具有高协同性和低分散性指数的共聚反应。定量的单分子剖析方法表明，含有衔接子的 DHT 基序的催化打开触发了连续的分支迁移，该迁移自动传播以形成具有交替基元的共聚物。我们发现，这些形状定义的超分子纳米结构成为活的哺乳动物细胞以刚度依赖性方式有效内吞的底物。因此，这种类似于 catassembly 的体外重建方法为理解生理和病理条件下生物纤维的结构-功能关系提供了线索。
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