27 March 2015

An ion channel made from DNA

by Kerstin Göpfrich

 

We created the smallest membrane-inserting DNA nanostructure to date, approaching the dimensions of natural ion channels.

Ion channels are present in every living cell. They are sophisticated gatekeepers bridging the cell membrane, the envelope surrounding a cell. If a channel is open, ions can be transported in and out of the cell, the basic process of nerve conduction and other metabolic activities. By creating synthetic ion channels, researchers hope to gain a deeper understanding of their natural counterparts, since malfunctioning channels

are a common cause of disease. Synthetic channels could further be used to deliver drugs inside a cell or to replace a defect.

First approaches to create synthetic channels date back to the 1970s, but their chemical synthesis is difficult and making diverse channel architectures remains challenging. With the recent advances in DNA nanotechnology, our membrane-inserting DNA nanostructure presented in the journal Nanoletters in March 2015 overcomes these drawbacks.

We designed a simple DNA nanostructure from eight short DNA sequences, two of which carry modifications for membrane anchoring. These sequences can be ordered online and synthesized for just a few pounds. Upon mixing them, the structure self-assembles into a bundle of four interconnected DNA double-helices with a sub-nanometer channel in the middle. These dimensions match typical ion channels. A major advantage of this DNA nanostructure is that its creation is scalable and requires virtually no equipment: Assembly and membrane attachment happen at room temperature within a minute.

Albeit its simple design, the novel DNA nanostructure shows the main characteristics of its natural counterparts. We can even observe it open and close when embedded in the membrane in response to the applied voltage. This behaviour is reminiscent of gating which natural ion channels exhibit.

Since the diameter of our nanostructure is much smaller than that of previous DNA nanopores, it offers exciting new opportunities for ion selectivity, an important feature of natural channels. Instead of transporting every type of ion, nature has developed mechanisms by which its channels can distinguish two different types of ions, even if they are almost the same size.  Using DNA nanotechnology and our sub-nanometer channel, we are a step closer to engineer the first highly ion-selective synthetic channel. And this, I am convinced, would be an exciting new tool in biomedicine!

 

Read the full article in Nanoletters  here.