A Plasma Membrane Polarity Sensor Harnessing Conjoined Twisted Intramolecular Charge Transfer Modulation and Charge Number Control Strategy

Polarity is a critical microenvironmental factor of the plasma membrane, which can offer valuable insights into various biological processes. Herein, we proposed a novel strategy for the construction of fluorescent agents to measure plasma membrane polarity by conjoining twisted intramolecular charge transfer (TICT) modulation and charge number control. It is shown that compounds with a stronger TICT tendency are more sensitive to polarity shifts due to the number of dialkylated amino groups present (from 1 to 3), and the molecules with two or more charged centers remain in the plasma membrane. Therefore, we developed two fluorescent agents with high polarity sensitivity, excellent turn-on ratios, and superior ability, to target the plasma membrane. In the wash-free fluorescence imaging and fluorescence lifetime tests, our designed agent could detect plasma membrane polarity with high precision, allowing effective distinction between cancer cells and normal cells based on their differences in plasma membrane polarity. Moreover, both fluorescence and fluorescence lifetime changes of the plasma membrane in the ferroptosis model established by Sorafenib confirmed an increase in plasma membrane polarity during cell ferroptosis.