Mapping cisplatin-induced viscosity alterations in cancer cells using molecular rotor and fluorescence lifetime imaging microscopy.

Abstract:

SIGNIFICANCE:Despite the importance of the cell membrane in regulation of drug activity, the influence of drug treatments on its physical properties is still poorly understood. The combination of fluorescence lifetime imaging microscopy (FLIM) with specific viscosity-sensitive fluorescent molecular rotors allows the quantification of membrane viscosity with high spatiotemporal resolution, down to the individual cell organelles. AIM:The aim of our work was to analyze microviscosity of the plasma membrane of living cancer cells during chemotherapy with cisplatin using FLIM and correlate the observed changes with lipid composition and cell's response to treatment. APPROACH:FLIM together with viscosity-sensitive boron dipyrromethene-based fluorescent molecular rotor was used to map the fluidity of the cell's membrane. Chemical analysis of membrane lipid composition was performed with time-of-flight secondary ion mass spectrometry (ToF-SIMS). RESULTS:We detected a significant steady increase in membrane viscosity in viable cancer cells, both in cell monolayers and tumor spheroids, upon prolonged treatment with cisplatin, as well as in cisplatin-adapted cell line. ToF-SIMS revealed correlative changes in lipid profile of cisplatin-treated cells. CONCLUSIONS:These results suggest an involvement of membrane viscosity in the cell adaptation to the drug and in the acquisition of drug resistance.

journal_name

J Biomed Opt

authors

Shimolina LE,Gulin AA,Paez-Perez M,López-Duarte I,Druzhkova IN,Lukina MM,Gubina MV,Brooks NJ,Zagaynova EV,Kuimova MK,Shirmanova MV

doi

10.1117/1.JBO.25.12.126004

subject

Has Abstract

pub_date

2020-12-01 00:00:00

issue

12

eissn

1083-3668

issn

1560-2281

pii

JBO-200248R

journal_volume

25

pub_type

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