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Ochmann, Sarah E.; Joshi, Himanshu; Bueber, Ece; Franquelim, Henri G.; Stegemann, Pierre; Sacca, Barbara; Keyser, Ulrich F.; Aksimentiev, Aleksei und Tinnefeld, Philip (2021): DNA Origami Voltage Sensors for Transmembrane Potentials with Single-Molecule Sensitivity. In: Nano Letters, Bd. 21, Nr. 20: S. 8634-8641

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Abstract

Signal transmission in neurons goes along with changes in the transmembrane potential. To report them, different approaches, including optical voltage-sensing dyes and genetically encoded voltage indicators, have evolved. Here, we present a DNA nanotechnology-based system and demonstrated its functionality on liposomes. Using DNA origami, we incorporated and optimized different properties such as membrane targeting and voltage sensing modularly. As a sensing unit, we used a hydrophobic red dye anchored to the membrane and an anionic green dye at the DNA to connect the nanostructure and the membrane dye anchor. Voltage-induced displacement of the anionic donor unit was read out by fluorescence resonance energy transfer (FRET) changes of single sensors attached to liposomes. A FRET change of similar to 5% for Delta Psi = 100 mV was observed. The working mechanism of the sensor was rationalized by molecular dynamics simulations. Our approach holds potential for an application as nongenetically encoded membrane sensors.

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