Probing cell membrane damage using a molecular rotor probe with membrane-to-nucleus translocation

Abstract

Damage to cell membranes, the outermost protection layer, is fatal to cells. However, precisely monitoring and in situ reporting cell membrane damage is not trivial. Herein, we present a molecular rotor probe, TPAE2, which can effectively bind to DNA and 1,2-dioleoyl-sn-glycero-3-phosphocholine in solution. Due to the light-up imaging characteristics of the molecular rotor, TPAE2 offers ultrafast and wash-free staining of plasma membrane with 160-fold fluorescence “turn-on” and excellent photostability. Once the membrane is damaged, TPAE2 can light-up the nucleus as a signal reporter. The cascade imaging of the cell membrane and nucleus using TPAE2 enabled real-time tracking of the whole process of cell apoptosis. What's more, under irradiation, TPAE2 stained on the cell membrane could penetrate cells rapidly and selectively stain the nucleus, self-reporting the cancer cell ablation process. This is the first example that a single molecule with multiple functions can light up the nucleus as an indication of cell membrane damage. The membrane-to-nucleus translocation strategy opens up a new avenue for the design of membrane damage diagnosis probes for biomedical applications.