Designer piercings: New membrane pores with DNA nanotechnology

Nov 04, 2013

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 are notoriously difficult to handle due to the complex and often unpredictable ways in which their structures can fold. Even minor 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 , a key challenge had to be addressed: the water-soluble DNA-based will not embed itself into the greasy membrane which is composed of lipids.

To overcome this, the scientists chemically attached to the DNA tube two large anchors, made of molecules which have a natural affinity for lipids. These structures were then able to embed the tube into the membrane. These structures, which are based on naturally derived porphyrins, were designed by a group led by Dr Eugen Stulz (University of Southampton).

"Porphyrin have ideal characteristics for our purposes," Stulz explains. "They are a strong membrane anchor, which locks the nanopore securely into the lipid membrane. In addition, they are fluorescent, which means they are easy to see and study. This makes them superior to other technologies."

The pores were characterised with electrical and fluorescence measurements in collaboration with Dr Ulrich Keyser (Cavendish Laboratory, Cambridge).

The simplicity of self-assembling a structure with only two anchors (previous studies used 26 or even 72 such anchors) greatly streamlines the design and synthesis of nanopores.

"In future, this new process will enable us to tailor DNA nanopores for a much wider range of applications than are currently possible," Keyser says.

The ability to create synthetic channels through lipid membranes enables numerous applications in the life sciences. In the first instance, DNA nanopores are of great interest for biosensing, such as rapid DNA analysis.

But tailored pores can also be expected to aid the development of new drugs. Prototype drugs are typically designed to affect a biological target, but are not engineered to cross the cell . Self-assembled provide a route for drugs to pass into cells, allowing for much faster pre-clinical screening for activity.

Explore further: Nanopore opens new cellular doorway for drug transport

More information: onlinelibrary.wiley.com/doi/10.1002/anie.201308381/abstract

Related Stories

Nanopore opens new cellular doorway for drug transport

Oct 23, 2013

A living cell is built with barriers to keep things out – and researchers are constantly trying to find ways to smuggle molecules in.‬ ‪Professor Giovanni Maglia (Biochemistry, Molecular and Structural ...

New system to improve DNA sequencing

Apr 03, 2013

(Phys.org) —A sensing system developed at Cambridge is being commercialised in the UK for use in rapid, low-cost DNA sequencing, which would make the prediction and diagnosis of disease more efficient, ...

Proteins in their natural habitat

Oct 29, 2013

Proteins which reside in the membrane of cells play a key role in many biological processes and provide targets for more than half of current drug treatments. These membrane proteins are notoriously difficult ...

Advance in nanotech gene sequencing technique

May 20, 2013

(Phys.org) —The allure of personalized medicine has made new, more efficient ways of sequencing genes a top research priority. One promising technique involves reading DNA bases using changes in electrical ...

Artificial ion channels created using DNA origami

Nov 16, 2012

(Phys.org)—Researchers in Germany and the US have used scaffolded DNA origami techniques to create ion channels or pores that span and penetrate lipid membranes and mimic natural ion channels.

Recommended for you

Thinnest feasible nano-membrane produced

12 hours ago

A new nano-membrane made out of the 'super material' graphene is extremely light and breathable. Not only can this open the door to a new generation of functional waterproof clothing, but also to ultra-rapid filtration. The ...

Wiring up carbon-based electronics

15 hours ago

Carbon-based nanostructures such as nanotubes, graphene sheets, and nanoribbons are unique building blocks showing versatile nanomechanical and nanoelectronic properties. These materials which are ordered ...

User comments : 0

More news stories

Thinnest feasible nano-membrane produced

A new nano-membrane made out of the 'super material' graphene is extremely light and breathable. Not only can this open the door to a new generation of functional waterproof clothing, but also to ultra-rapid filtration. The ...

Wiring up carbon-based electronics

Carbon-based nanostructures such as nanotubes, graphene sheets, and nanoribbons are unique building blocks showing versatile nanomechanical and nanoelectronic properties. These materials which are ordered ...

Better thermal-imaging lens from waste sulfur

Sulfur left over from refining fossil fuels can be transformed into cheap, lightweight, plastic lenses for infrared devices, including night-vision goggles, a University of Arizona-led international team ...

Hackathon team's GoogolPlex gives Siri extra powers

(Phys.org) —Four freshmen at the University of Pennsylvania have taken Apple's personal assistant Siri to behave as a graduate-level executive assistant which, when asked, is capable of adjusting the temperature ...