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DNA membrane channels

Membrane protein channels involved in cellular signal transductions are fascinating biological sensors with high selectivity and efficiency. Recently, DNA origami nanostructures emerged as highly customizable mimetics of biological membrane channels. A typical DNA membrane channel is assembled from several DNA double helices arranged into a polygon pattern, with the central cavity forming the transmembrane pore. To facilitate insertion of the DNA channel into a lipid bilayer membrane, the DNA helices are chemically modified to carry hydrophobic anchors. Until now, most of the DNA channels featured four or six DNA helices arranged in a square or a hexagon, with the inner channel diameter varying between 1 and 2.5 nm. Using all-atom Molecular Dynamics (MD) simulation, we characterized the biophysical properties of the DNA membrane channels with atomic precision. We further engineered DNA membrane channels that span one order of magnitude in diameter and three orders of magnitude in conductance and molecular weight, covering the entire range of the protein membrane channels.

Kerstin Göpfrich*, Chen-Yu Li*, Maria Ricci, Satya Prathyusha Bhamidimarri, Jejoong Yoo, Bertalan Gyenes, Alexander Ohmann, Mathias Winterhalter, Aleksei Aksimentiev, and Ulrich F. Keyser ACS Nano (2016)

DNA nanotechnology allows for the creation of three-dimensional structures at nanometer scale. Here, we use DNA to build the largest synthetic pore in a lipid membrane to date, approaching the dimensions of the nuclear pore complex and increasing the pore-area and the conductance tenfold compared to previous man-made channels. In our design, nineteen cholesterol-tags anchor a megadalton funnel-shaped DNA origami porin in a lipid bilayer membrane (see equilibration trajectory, require login to nanoHUB). Confocal imaging and ionic current recordings reveal spontaneous insertion of the DNA porin into the lipid membrane, creating a transmembrane pore of tens of nanosiemens conductance (see ionic current trajectory). All-atom molecular dynamics simulations characterize the conductance mechanism at the atomic level and independently confirm the DNA porins' large ionic conductance.

Kerstin Göpfrich, Chen-Yu Li, Iwona Mames, Satya Prathyusha Bhamidimarri, Maria Ricci, Jejoong Yoo, Adam Mames, Alexander Ohmann, Mathias Winterhalter, Eugen Stulz, Aleksei Aksimentiev, and Ulrich F. Keyser Nano Letters (2016)

Due to 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 (see water channel trajectory, require login to nanoHUB). Ions flow (see ion transport trajectory) at the DNA-lipid interface as the lipid head groups tilt towards 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.

Jejoong Yoo, and Aleksei Aksimentiev The Journal of Physical Chemistry Letters (2015)

DNA self-assembly has emerged as a new paradigm for design of biomimetic membrane channels. Several experimental groups have already demonstrated assembly and insertion of DNA channels into lipid bilayer membranes; however, the structure of the channels and their conductance mechanism have remained undetermined. Here, we report the results of molecular dynamics simulations that characterized the biophysical properties of the DNA membrane channels with atomic precision. We show that, while overall remaining stable, the local structure of the channels undergoes considerable fluctuations, departing from the idealized design. The transmembrane ionic current flows both through the central pore of the channel as well as along the DNA walls and through the gaps in the DNA structure. Surprisingly, we find that the conductance of DNA channels depend on the membrane tension, making them potentially suitable for force-sensing applications. Finally, we show that electro-osmosis governs the transport of druglike molecules through the DNA channels.