“LEGO-like” technique gives insight into DNA transport through nanopores

When we think of polymers, most of us picture the polyester found in so many of our clothes, the polyethylene used in food packaging or the Teflon used to make our non-stick cookware. However, polymers are also found in nature – in cellulose, proteins and even DNA.

Polymers are defined as large molecules made up of long chains of smaller molecules. When transported inside and between cells, polymers such as DNA must pass through nanometre-sized pores, or nanopores. Besides underpinning many biological processes, the transport of polymers is also the basis for a wide range of sensing technologies used for DNA single-molecule detection and sequencing.

Researchers supported in part by the EU-funded DesignerPores project have now developed a new technique to measure how the velocity of DNA changes as it moves through a nanopore. Their study has been published in ‘Nature Physics’.

Dubbed “LEGO-like” in a news item posted on ‘Phys.org’, the technique involves “assembling DNA molecules that have protruding bumps at specific locations along their length.” The research team passed the molecules through a nanopore and observed how the ion flow pattern changed. This allowed them to see precisely how the DNA’s velocity changed during the process.

The results revealed two stages of behaviour. At first, the DNA slowed down as it moved through the nanohole, but then it accelerated as it drew close to the end of the process. Simulations indicated that the DNA’s behaviour changed as the friction between the polymer and the surrounding fluid altered.“Our method for assembling LEGO-like molecular DNA rulers has given new insight into the process of threading polymers through incredibly small holes just a few nanometres in size,” observed senior author Dr Nicholas Bell from the Cavendish Laboratory at DesignerPores project host University of Cambridge. “The combination of both experiments and simulations have revealed a comprehensive picture of the underlying physics of this process and will aid the development of nanopore-based biosensors. It is very exciting that we can now measure and understand these molecular processes in such minute detail.”

According to lead author Dr Kaikai Chen, also from the Cavendish Laboratory, “these results will help improve the accuracy of nanopore sensors in their various applications, for instance localizing specific sequences on DNA with nanometer accuracy or detecting diseases early with target RNA detection.”

Dr Chen went on to explain: “The superior resolution in analyzing molecules passing through nanopores will allow for low-error decoding of digital information stored on DNA. We are exploring and improving the utility of nanopore sensors for these applications.”

The research team also comprised scientists from the University of Massachusetts in the United States. The 6-year DesignerPores (Understanding and Designing Novel NanoPores) project ended in June 2021.

For more information, please see:

DesignerPores project