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Highly shape- and size-tunable membrane nanopores made with DNA
Yongzheng Xing1, Adam Dorey1, Lakmal Jayasinghe2
1Department of Chemistry & Institute of Structural Molecular Biology, University College London, London, UK.
Nature Nanotechnology
|April 28, 2022
Summary
DNA nanotechnology enables the creation of custom membrane nanopores with tunable shapes and sizes up to tens of nanometers. These designer nanopores facilitate direct single-molecule sensing for applications in diagnostics and biophysical analysis.
Area of Science:
- Biotechnology
- Nanotechnology
- Synthetic Biology
Background:
- Membrane nanopores are crucial for biological molecular transport, DNA sequencing, and single-molecule analysis.
- Existing nanopores are limited to narrow widths, while wider, tunable structures are highly desired but challenging to engineer.
- Nature does not provide wide nanopores, and current de novo protein engineering methods face limitations.
Purpose of the Study:
- To demonstrate that rational DNA design can significantly expand the structural and functional capabilities of membrane nanopores.
- To engineer custom nanopores with tunable shapes and lumen widths exceeding those found in nature.
- To showcase the utility of these designer nanopores for advanced molecular sensing applications.
Main Methods:
- A DNA nanotechnology approach was employed, bundling DNA duplexes into modular pore subunits.
- These subunits were arranged to form nanopores with controllable shapes and widths up to tens of nanometers.
- Functional units for recognition and signaling were optionally integrated into the nanopore structures.
Main Results:
- Successfully engineered custom membrane nanopores with tunable shapes and lumen widths up to tens of nanometers.
- Demonstrated direct single-molecule electrical sensing of 10-nm proteins using these designer nanopores.
- Validated the utility of the nanopores with both standard research equipment and portable analysis devices.
Conclusions:
- DNA nanotechnology offers a powerful platform for creating novel membrane nanopores with unprecedented structural diversity.
- Custom-engineered nanopores can be utilized for sensitive, label-free single-molecule analysis and direct electrical sensing.
- These designer nanopores hold significant potential for synthetic biology, biophysical analysis, portable diagnostics, and environmental screening.

