Imaging plasma membrane microviscosity in cancer cells during chemotherapy

Recent studies suggest that cancer cell response to cisplatin can not be fully described in terms of only interaction of the drug with DNA, but can include effects associated with other cellular targets. The study of effects of chemotherapeutic drugs on the viscosity of plasma membrane is important for better understanding the mechanisms of the drug action and evaluating the effectiveness of therapy. The aim of this work was to analyze microviscosity of plasma membrane of cancer cells during chemotherapy with cisplatin. For imaging viscosity at the microscopic level fluorescent molecular rotor BODIPY2 and fluorescence lifetime imaging microscopy (FLIM) were used. We detected a significant increase in membrane viscosity in viable human cervical cancer cells HeLa, both in cell monolayer and tumor spheroids after cisplatin treatment. Measuring viscosity in cisplatin-resistant cell line showed that viscosity increases when cells acquire chemoresistance. These results suggest that microviscosity of membrane plays a role in the cytotoxicity of cisplatin and its mapping may provide a powerful tool for investigation of tumor responses to chemotherapy and mechanisms of drug resistance.