Depending on electron-withdrawing enhancement to design an environment-sensitive fluorescent probe with high fidelity for imaging viscosity in lipid droplets

Lipid droplet (LD) viscosity plays an important role in maintaining LD homeostasis. The disruption of viscosity could lead to LD dysfunction, then cell lesion and death. Visualizing the LD viscosity with high fidelity is essential for further understanding its detailed physiological and pathological functions. In this study, we developed a novel neutral fluorescence probe TC-P for sensing viscosity in LDs with high signal-to-noise ratio. By introducing benzothiazole-2-acetonitrile, a strong electron withdrawing group, probe TC-P showed sensitive viscosity responses, high selectivity and photo-stability in the spectral tests. Owing to its lipophilicity and viscosity response properties, TC-P has targeted into LDs with high signal-to-noise ratio compared with BODIPY 493/503. Furthermore, TC-P has achieved in imaging the LD viscosity with high fidelity after the treatment of monensin and induction of ferroptosis. Therefore, TC-P is a potential molecular tool for tracing LD viscosity to unveil its complex roles.