Probing Cell Membrane Damage using Molecular Rotor Probe with Membrane-to-Nucleus Translocation

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.