DNA enzyme shuffles cell membranes a thousand times faster than its natural counterpart


22-06-2018

A new synthetic enzyme, crafted from DNA rather than protein, ‘flips’ lipid molecules within the cell membrane, triggering a signal pathway that could be harnessed to induce cell death in cancer cells.

This work highlights the enormous potential of synthetic DNA nanostructures for personalised drugs and therapeutics for a variety of health conditions.
- Alexander Ohmann

Researchers at the University of Cambridge and the University of Illinois at Urbana-Champaign say their lipid-scrambling DNA enzyme is the first to outperform naturally occurring enzymes – and does so by three orders of magnitude. Their findings are published in the journal Nature Communications.

“Cell membranes are lined with a different set of molecules on the inside and outside, and cells devote a lot of resources to maintaining this,” said study leader Aleksei Aksimentiev, a professor of physics at Illinois. “But at some points in a cell’s life, the asymmetry has to be dismantled. Then the markers that were inside become outside, which sends signals for certain processes, such as cell death. There are enzymes in nature that do that called scramblases. However, in some other diseases where scramblases are deficient, this doesn’t happen correctly. Our synthetic scramblase could be an avenue for therapeutics.”

Aksimentiev’s group came upon DNA’s scramblase activity when looking at DNA structures that form pores and channels in cell membranes. They used the Blue Waters supercomputer at the National Center for Supercomputing Applications at Illinois to model the systems at the atomic level. They saw that when certain DNA structures insert into the membrane – in this case, a bundle of eight strands of DNA with cholesterol at the ends of two of the strands – lipids in the membrane around the DNA begin to shuffle between the inner and outer membrane layers.

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Image: DNA scramblase

Credit: Aleksei Aksimentiev

Reproduced courtesy of the University of Cambridge

 

The University of Cambridge is acknowledged as one of the world's leading higher education and research institutions. The University was instrumental in the formation of the Cambridge Network and its Vice- Chancellor, Professor Stephen Toope, is also the President of the Cambridge Network.

University of Cambridge (cam.ac.uk)