Monday, 06 December, 2021

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

Sarah E. Ochmann, H. Joshi, E. Buber, Henri G. Franquelim, P. Stegemann, B. Sacca, Ulrich F. Keyser, A. Aksimentiev, P. Tinnefeld

10.1021/acs.nanolett.1c02584

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.

www.webofscience.com/wos/woscc/full-record/WOS:000713060900014