A synthetic enzyme built from DNA flips 107 lipids per second in biological membranes

Alexander Ohmann, Chen-Yu Li, Christopher Maffeo, Kareem Al Nahas, Kevin N. Baumann, Kerstin Göpfrich, Jejoong Yoo, Ulrich F. Keyser () and Aleksei Aksimentiev ()
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Alexander Ohmann: University of Cambridge
Chen-Yu Li: University of Illinois at Urbana-Champaign
Christopher Maffeo: University of Illinois at Urbana-Champaign
Kareem Al Nahas: University of Cambridge
Kevin N. Baumann: University of Cambridge
Kerstin Göpfrich: University of Cambridge
Jejoong Yoo: University of Illinois at Urbana-Champaign
Ulrich F. Keyser: University of Cambridge
Aleksei Aksimentiev: University of Illinois at Urbana-Champaign

Nature Communications, 2018, vol. 9, issue 1, 1-9

Abstract: Abstract Mimicking enzyme function and increasing performance of naturally evolved proteins is one of the most challenging and intriguing aims of nanoscience. Here, we employ DNA nanotechnology to design a synthetic enzyme that substantially outperforms its biological archetypes. Consisting of only eight strands, our DNA nanostructure spontaneously inserts into biological membranes by forming a toroidal pore that connects the membrane’s inner and outer leaflets. The membrane insertion catalyzes spontaneous transport of lipid molecules between the bilayer leaflets, rapidly equilibrating the lipid composition. Through a combination of microscopic simulations and fluorescence microscopy we find the lipid transport rate catalyzed by the DNA nanostructure exceeds 107 molecules per second, which is three orders of magnitude higher than the rate of lipid transport catalyzed by biological enzymes. Furthermore, we show that our DNA-based enzyme can control the composition of human cell membranes, which opens new avenues for applications of membrane-interacting DNA systems in medicine.

Date: 2018
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DOI: 10.1038/s41467-018-04821-5

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