The Role of Plasma Membrane Viscosity in the Response and Resistance of Cancer Cells to Oxaliplatin

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2021 Dec 24

PMID 34944789

Citations 12

Authors

Liubov Shimolina

Alexander Gulin

Nadezhda Ignatova

Irina Druzhkova

Margarita Gubina

Maria Lukina

Ludmila Snopova

Elena Zagaynova

Marina K Kuimova

Marina Shirmanova

Affiliations

Soon will be listed here.

Abstract

Maintenance of the biophysical properties of membranes is essential for cell survival upon external perturbations. However, the links between a fluid membrane state and the drug resistance of cancer cells remain elusive. Here, we investigated the role of membrane viscosity and lipid composition in the responses of cancer cells to oxaliplatin and the development of chemoresistance. Plasma membrane viscosity was monitored in live colorectal cancer cells and tumor xenografts using two-photon excited fluorescence lifetime imaging microscopy (FLIM) using the fluorescent molecular rotor BODIPY 2. The lipid profile was analyzed using time-of-flight secondary ion mass spectrometry (ToF-SIMS). It was found that the plasma membrane viscosity increased upon oxaliplatin treatment, both in vitro and in vivo, and that this correlated with lower phosphatidylcholine and higher cholesterol content. The emergence of resistance to oxaliplatin was accompanied by homeostatic adaptation of the membrane lipidome, and the recovery of lower viscosity. These results suggest that maintaining a constant plasma membrane viscosity via remodeling of the lipid profile is crucial for drug resistance in cancer.

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