Strategic Communications and Marketing News Bureau

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

CHAMPAIGN, Ill. — 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 University of Illinois at Urbana-Champaign and the University of Cambridge say their lipid-scrambling DNA enzyme is the first in its class to outperform naturally occurring enzymes – and does so by three orders of magnitude. They published their findings in the journal Nature Communications.

Postdoctoral researcher Christopher Maffeo and physics professor Aleksei Aksimentiev used the Blue Waters supercomputer to model synthetic DNA enzymes.

Postdoctoral researcher Christopher Maffeo and physics professor Aleksei Aksimentiev used the Blue Waters supercomputer to model synthetic DNA enzymes.

“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 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.

See an animation at https://youtu.be/kGgTIFYbUko.

To verify the scramblase activity predicted by the computer models, Aksimentiev’s group at Illinois partnered with professor Ulrich Keyser’s group at Cambridge. The Cambridge group 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 paper along with Illinois graduate student Chen-Yu Li. “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.”

Chen-Yu Li, who recently graduated from Aksimentievs group, was the co-first author of the paper.

Chen-Yu Li, who recently graduated from Aksimentiev’s group, was the co-first author of the paper.

On its own, the DNA scramblase produces cell death indiscriminately, Aksimentiev said. The next step is to couple it with targeting systems that specifically seek out certain cell types, a number of which have already been developed for other DNA agents.

“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.

“Although we have still a long way to go, this work highlights the enormous potential of synthetic DNA nanostructures with possible applications for personalized drugs and therapeutics for a variety of health conditions in the future,” Ohmann said.

The U.S. National Science Foundation and the National Institutes of Health supported this work.  

Editor’s notes: To reach Aleksei Aksimentiev, call 217-333-6495; email aksiment@illinois.edu.  To reach Ulrich Keyser, call +44 (0)1223 337272; email ufk20@cam.ac.uk.

The paper “A synthetic enzyme built from DNA flips 107 lipids per second in biological membranes” is available online. DOI: 10.1038/s41467-018-04821-5

Read Next

Life sciences Portrait of the research team posing together.

Minecraft players can now explore whole cells and their contents

CHAMPAIGN, Ill. — Scientists have translated nanoscale experimental and computational data into precise 3D representations of bacteria, yeast and human epithelial, breast and breast cancer cells in Minecraft, a video game that allows players to explore, build and manipulate structures in three dimensions. The innovation will allow researchers and students of all ages to navigate […]

Arts Photo of seven dancers onstage wearing blue tops and orange or yellow flowing skirts. The backdrop is a Persian design.

February Dance includes works experimenting with live music, technology and a ‘sneaker ballet’

CHAMPAIGN, Ill. — The dance department at the University of Illinois Urbana-Champaign will present February Dance 2025: Fast Forward this week at Krannert Center for the Performing Arts. February Dance will be one of the first performances in the newly renovated Colwell Playhouse Theatre since its reopening. The performances are Jan. 30-Feb. 1. Dance professor […]

Honors portraits of four Illinois researchers

Four Illinois researchers receive Presidential Early Career Award

CHAMPAIGN, Ill. — Four researchers at the University of Illinois Urbana-Champaign were named recipients of the Presidential Early Career Award for Scientists and Engineers, the highest honor bestowed by the U.S. government on young professionals at the outset of their independent research careers. The winners this year are health and kinesiology professor Marni Boppart, physics professor Barry Bradlyn, chemical and biomolecular engineering professor Ying […]

Strategic Communications and Marketing News Bureau

507 E. Green St
MC-426
Champaign, IL 61820

Email: stratcom@illinois.edu

Phone (217) 333-5010