Small-molecule fluorescent probes for plasma membrane staining: Design, mechanisms and biological applications

Plasma membrane (PM), a phospholipid bilayer that separates the interior of cell from the extracellular fluid, is closely involved in various cellular activities. However, monitoring dynamic membrane has always been a challenge due to its dynamic structure and complex constitution. Owing to the distinct advantages of fluorescence imaging technology, diverse small molecular fluorescent probes have been well developed for membrane staining to investigate membrane function and monitor its dynamic activity. Herein, representative small molecular fluorescent probes reported in the last ten years were summarized and categorized into four groups according to their functional membrane-anchoring moieties, namely hydrophobic alkyl chain, ammonium unit, cholesterol, and short peptide sequence. In particular, the underlying mechanisms to achieve membrane-specific fluorescence staining were fully discussed, including membrane targeting group approach, aggregation induced emission (AIE), disassembly light up fluorescence strategy and restricted intramolecular rotation (RIM). Furthermore, membrane-targeting probes for super-resolution imaging of membrane dynamics were presented as an emerging technology. In this review, we showcased recent advances in this research area, and outlined potential challenges and prospects with the goal of driving the generation of innovative fluorescent probes for PM staining.