Authors
Pranamita Chakraborti, Rui Fu, Lucia M Wert, Charlie A L Darby, Joy D Amuzu, Daphne Oettinger, Aditya Nandy, Yamuna Krishnan, Michael G Walter
Published in
Chemical science. Aug 25, 2026. Epub Aug 25, 2026.
Abstract
Voltage sensitive dyes (VSDs) are versatile and powerful reporters of the membrane potential across cell membranes. Thiazolothiazole (TTz) dyes are a promising new class of VSDs with high photostability and low cytotoxicity. However, the mechanistic basis of their voltage sensitivity is unknown. To address this, we developed a new generation of asymmetrically substituted TTz dyes (asym-TTz). They exhibit strong solvatofluorochromism with large Stokes shifts and exceptionally large changes in dipole moments (23-29 D), representing an 80% increase over those of previously reported TTz VSDs. An asym-TTz derivative, TwistTz-P, bearing a carboxyphenyl acceptor group, shows sustained cellular membrane localization and a voltage sensitivity of ∼10% ΔF/F per 100 mV. Computational analysis of TwistTz-P under varying electric fields revealed a pronounced twist on both sides of the TTz bridging unit in the excited state. The degree of twisting was voltage-dependent, exhibiting an increase upon depolarization, consistent with the experimentally observed fluorescence decrease at an identical voltage. In another asym-TTz dye (FlatTz-P), where a carboxypyrazinyl acceptor group was incorporated, excited-state twisting under varying electric fields was negligible and demonstrated no voltage sensitivity. These observations establish electric field-dependent excited-state twisting as a new voltage sensing mechanism, and, additionally, provide a new strategy for creating highly sensitive VSDs.
PMID:
42781324
Bibliographic data and abstract were imported from PubMed on 25 Sep 2026.
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