Ion Channels Made from a Single Membrane-Spanning DNA Duplex.

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Göpfrich, Kerstin 
Li, Chen-Yu 
Mames, Iwona 
Bhamidimarri, Satya Prathyusha 
Ricci, Maria 

Because of their hollow interior, transmembrane channels are capable of opening up pathways for ions across lipid membranes of living cells. Here, we demonstrate ion conduction induced by a single DNA duplex that lacks a hollow central channel. Decorated with six porpyrin-tags, our duplex is designed to span lipid membranes. Combining electrophysiology measurements with all-atom molecular dynamics simulations, we elucidate the microscopic conductance pathway. Ions flow at the DNA-lipid interface as the lipid head groups tilt toward the amphiphilic duplex forming a toroidal pore filled with water and ions. Ionic current traces produced by the DNA-lipid channel show well-defined insertion steps, closures, and gating similar to those observed for traditional protein channels or synthetic pores. Ionic conductances obtained through simulations and experiments are in excellent quantitative agreement. The conductance mechanism realized here with the smallest possible DNA-based ion channel offers a route to design a new class of synthetic ion channels with maximum simplicity.

DNA nanotechnology, lipid membrane, molecular dynamics, porphyrin, synthetic ion channel, DNA, Ion Channel Gating, Ion Channels, Ion Transport, Lipid Bilayers, Molecular Dynamics Simulation
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Nano Lett
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American Chemical Society (ACS)
European Research Council (647144)
European Research Council (261101)
K.G. acknowledges funding from the Winton Programme for the Physics of Sustainability, Gates Cambridge, and the Oppenheimer Ph.D. studentship, U.F.K. from an ERC starting Grant Passmembrane 261101 and Oxford Nanopore Technologies, and M.R. from the Early Postdoc Mobility fellowship of the Swiss National Science Foundation. A.A., J.Y., and C.Y.L. acknowledge support form the National Science Foundation under Grants DMR-1507985, PHY-1430124, and EEC-1227034 and the supercomputer time provided through XSEDE Allocation Grant MCA05S028 and the Blue Waters petascale supercomputer system (UIUC). M.W. and S.P.B. acknowledge support from Marie Skłodowska Curie Actions within the Initial Training Networks Translocation Network, project no. 607694 and I.M. from the Marie Skłodowska Curie Fellowship “Nano-DNA” (FP7-PEOPLE-2012-IEF, No 331952).