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DNA Origami Voltage Sensors for Transmembrane Potentials with Single-Molecule Sensitivity

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Franquelim,  Henri G.
Schwille, Petra / Cellular and Molecular Biophysics, Max Planck Institute of Biochemistry, Max Planck Society;

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Citation

Ochmann, S. E., Joshi, H., Bueber, E., Franquelim, H. G., Stegemann, P., Sacca, B., et al. (2021). DNA Origami Voltage Sensors for Transmembrane Potentials with Single-Molecule Sensitivity. Nano Letters, 21(20), 8634-8641. doi:10.1021/acs.nanolett.1c02584.


Cite as: https://hdl.handle.net/21.11116/0000-0009-9575-B
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.