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New Molecular Scaffolds for Fluorescent Voltage Indicators

preprint
submitted on 14.11.2018, 07:16 and posted on 14.11.2018, 14:13 by Steven Boggess, Shivaani Gandhi, Brian Siemons, Nathaniel Huebsch, Kevin Healy, Evan Miller

The ability to non-invasively monitor membrane potential dynamics in excitable cells like neurons and cardiomyocytes promises to revolutionize our understanding of the physiology and pathology of the brain and heart. Here, we report the design, synthesis, and application of a new class of fluorescent voltage indicator that makes use of a fluorene-based molecular wire as a voltage sensing domain to provide fast and sensitive measurements of membrane potential in both mammalian neurons and human-derived cardiomyocytes. We show that the best of the new probes, fluorene VoltageFluor 2 (fVF 2) readily reports on action potentials in mammalian neurons, detects perturbations to cardiac action potential waveform in human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes, shows a substantial decrease in phototoxicity compared to existing molecular wire-based indicators, and can monitor cardiac action potentials for extended periods of time. Together, our results demonstrate the generalizability of a molecular wire approach to voltage sensing and highlights the utility of fVF 2 for interrogating membrane potential dynamics.

History

Email Address of Submitting Author

evanwmiller@berkeley.edu

Institution

University of California, Berkeley

Country

United States of America

ORCID For Submitting Author

0000-0002-6556-7679

Declaration of Conflict of Interest

none to declare

Exports