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.

Researchers at the University of Illinois (UI) and the University of Cambridge say the lipid-scrambling DNA enzyme is the first in its class to outperform naturally occurring enzymes, and does so by three orders of magnitude.

The researchers 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 to model the systems at the atomic level, and saw that when certain DNA structures insert into the membrane, lipids in the membrane around the DNA begin to shuffle between the inner and outer membrane layers.

To verify the scramblase activity predicted by the computer models, UI researchers partnered with researchers at Cambridge, who synthesized the DNA enzyme and tested it in model membrane bubbles, called vesicles, and then in human breast cancer cells.

"The results show very conclusively that our DNA nanostructure indeed facilitates rapid lipid scrambling," said Alexander Ohmann, a graduate student at Cambridge and a co-first author of the study. "Most interestingly, the high flipping rate indicated by the molecular dynamics simulations seems to be of the same order of magnitude in experiments: up to a thousand-fold faster than what has previously been shown for natural scramblases."

The DNA scramblase produces cell death on its own indiscriminately, said study leader Aleksei Aksimentiev, a UI professor of physics. In the next step, the researchers will couple it with targeting systems that specifically seek out certain cell types.

"We are also working to make these scramblase structures activated by light or some other stimulus, so they can be activated only on demand and can be turned off," Aksimentiev said.

The findings have been published in the journal Nature Communications.