Directing curli polymerization with DNA origami nucleators

Xiuhai Mao, Ke Li, Mengmeng Liu, Xinyu Wang, Tianxin Zhao, Bolin An, Mengkui Cui, Yingfeng Li, Jiahua Pu, Jiang Li, Lihua Wang, Timothy K. Lu, Chunhai Fan () and Chao Zhong ()
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Xiuhai Mao: ShanghaiTech University
Ke Li: ShanghaiTech University
Mengmeng Liu: East China Normal University
Xinyu Wang: ShanghaiTech University
Tianxin Zhao: ShanghaiTech University
Bolin An: ShanghaiTech University
Mengkui Cui: ShanghaiTech University
Yingfeng Li: ShanghaiTech University
Jiahua Pu: ShanghaiTech University
Jiang Li: Chinese Academy of Sciences
Lihua Wang: Chinese Academy of Sciences
Timothy K. Lu: Massachusetts Institute of Technology
Chunhai Fan: Shanghai Jiao Tong University
Chao Zhong: ShanghaiTech University

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

Abstract: Abstract The physiological or pathological formation of fibrils often relies on molecular-scale nucleators that finely control the kinetics and structural features. However, mechanistic understanding of how protein nucleators mediate fibril formation in cells remains elusive. Here, we develop a CsgB-decorated DNA origami (CB-origami) to mimic protein nucleators in Escherichia coli biofilm that direct curli polymerization. We show that CB-origami directs curli subunit CsgA monomers to form oligomers and then accelerates fibril formation by increasing the proliferation rate of primary pathways. Fibrils grow either out from (departure mode) or towards the nucleators (arrival mode), implying two distinct roles of CsgB: as nucleation sites and as trap sites to capture growing nanofibrils in vicinity. Curli polymerization follows typical stop-and-go dynamics but exhibits a higher instantaneous elongation rate compared with independent fibril growth. This origami nucleator thus provides an in vitro platform for mechanistically probing molecular nucleation and controlling directional fibril polymerization for bionanotechnology.

Date: 2019
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DOI: 10.1038/s41467-019-09369-6

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