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The plasma membrane of cells is a crucial biological membrane that involved in a variety of cellular processes including cell signaling transduction through membrane electrical activity. Recently, monitoring membrane electrical activity using fluorescence imaging has attracted numerous attentions for its potential applications in evaluating how the nervous system works. However, the development of ideal fluorescent voltage-sensitive probes with both high membrane labeling efficiency and voltage sensitivity is still retain a big challenge. Herein, glutathione- capped CdSe@ZnS quantum dots (CdSe@ZnS-GSH QDs) with a size of 2.5 nm and an emission peak at 520 nm are synthesized using a facile ligand exchange method for plasma membrane labeling and membrane potential imaging. The as-synthesized CdSe@ZnS-GSH QDs can effectively label cell membrane at neutral pH within 30 min and exhibit excellent optical stability in continuous imaging for up to 60 min. With the test concentration up to 200 nM, CdSe@ZnS-GSH QDs show high biocompatibility to cells and do not affect cell proliferation, disturb cell membrane integrity or cause apoptosis and necrosis of cells. Then, a two-component voltage sensor strategy based on fluorescence resonance energy transfer (FRET) between CdSe@ZnS-GSH QDs and the dipicrylamine (DPA) is successfully developed to monitor the membrane potential by the fluorescence of CdSe@ZnS-GSH QDs. This study offers a facile strategy for labeling plasma membrane and monitoring the membrane potential of cells and will hold great potential in the research of signaling within intact neuronal circuits.
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