Water-Soluble Molecular Wires for Membrane Potential Imaging

用于膜电位成像的水溶性分子导线

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Abstract

Voltage-sensitive probes based on donor-acceptor dyads, whose fluorescence is modulated by photoinduced electron transfer (PET) in response to changes in membrane potential, are known as PET molecular wires. PET wires have been widely used in cultured cells; however, their applications in tissue-level imaging have been hampered by their inadequate aqueous solubility, necessitating pre-dissolution in organic solvents that potentially can cause toxic effects. Here we present the synthesis, electronic structure analysis, photophysical characterization, and initial demonstration of water-soluble amphiphilic molecular wires, consisting of a rosamine, as a fluorescent PET acceptor, and a PET donor consisting of a conjugated bridge terminated by dimethylaniline (DMA). The rosamine moiety is extended by several carboxylates or polyethylene glycol (PEG) groups, which render the probes highly water-soluble and facilitate labeling of phospholipid membranes, positioning molecules in proper orientation. The probes produced functional responses in electrically stimulated mouse cardiomyocytes and as well as in intact neurohypophysis, and in glucose-stimulated murine islets of Langerhans. The new molecular wires make up a useful addition to the toolkit of optical reporters for membrane potential imaging.

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