Designer piercings: New membrane pores with DNA nanotechnology

PUBLIC RELEASE DATE:

4-Nov-2013

Contact: Clare Ryan clare.ryan@ucl.ac.uk 44-020-310-83846 University College London

A new way to build membrane-crossing pores, using Lego-like DNA building blocks, has been developed by scientists at UCL, in collaboration with colleagues at the University of Cambridge and the University of Southampton.

The approach provides a simple and low cost tool for synthetic biology and the technique has potential applications in diagnostic devices and drug discovery. The research is featured in the current issue of the journal Angewandte Chemie.

Membrane pores are the gateways controlling the transport of essential molecules across the otherwise impermeable membranes that surround cells in living organisms. Typically made from proteins, pores of different sizes control the flow of ions and molecules both and in and out of the cell as part of an organism's metabolism.

Our understanding of membrane pores comes both from the study of both natural pores, and from equivalent structures built in the lab by synthetic biologists. But synthetic proteins are notoriously difficult to handle due to the complex and often unpredictable ways in which their structures can fold. Even minor protein misfolding changes a protein's properties, meaning that building synthetic pores out of proteins can be risky and time-consuming.

A more straightforward approach is so-called 'rational engineering' using Lego-like DNA building blocks. Although generally known as life's genetic code, DNA strands, which are chemically much simpler than proteins, are far easier and more predictable to work with than proteins. As such they are a useful material for building nanoscale structures in the lab.

"DNA is a construction material that follows very simple rules", said Dr Stefan Howorka (UCL Chemistry). "New nanostructures can be easily designed using a computer programme, and the elements fit together like Lego bricks. So we can build more or less whatever we like."

Using this approach, the team built a tiny tube measuring just 14 nanometres along and 5.5 nanometres across (around 10,000 times smaller than the width of a human hair). This formed the main part of their artificial nanopore. However, to insert the tube into a cell membrane, a key challenge had to be addressed: the water-soluble DNA-based structure will not embed itself into the greasy membrane which is composed of lipids.

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Designer piercings: New membrane pores with DNA nanotechnology