CC BY
2*
ALT'23 The 30th International Conference on Advanced Laser Technologies
B-I-30
Microviscosity of a cell membrane and is implication for cancer
treatment
L.E. Shimolina1, A.A. Gulin2, M.K. Kuimova3, I.N. Druzhkova1, N.I. Ignatova1, M.V.
Gubina2, A.E. Khlynova1, E.V. Zagaynova1 and M.V. Shirmanova1
1- Privolzhsky Research Medical University, Minin andPozharsky Square, 10/1, 603005 Nizhny Novgorod,
Russia;
2- Semenov Federal Research Center for Chemical Physics,of the Russian Academy of Sciences, Kosygina Str.
4, 117977Moscow, Russia;
3- Imperial College London, London SW7 2AZ, United Kingdom Shirmanovam@mail.ru
Viscosity, a reciprocal of fluidity, plays an important role in the functioning of living cells.
The microviscosity of the plasma membrane determines the activity of transporters and receptors, biosynthesis and catalytic activity of membrane enzymes, permeability to substances and the rate of diffusion, and much more. Microviscosity of cell membranes depends primarily on their lipid composition, specifically on cholesterol content, the ratio of saturated and unsaturated fatty acids and the length of the phospholipid tails. Despite the multiple roles of the microviscosity in cells, its significance for the response to chemotherapy is not fully understood.
Here, we developed methodology to measure microviscosity of cancer cells membrane in vitro and in vivo and investigated the changes in microviscosity and lipid composition upon chemotherapy and acquisition of drug resistance.
Plasma membrane viscosity was monitored in live cancer cells and tumor xenografts using two-photon excited fluorescence lifetime imaging microscopy (FLIM) using the viscosity-sensitive probe BODIPY 2 [1, 2]. The probe is a fluorescent molecular rotor that possesses sensitivity to a local viscosity due to conformational mobility. Viscous environment restricts conformational change of the rotor, which results in the increase of its fluorescence lifetime. The lipid profile of membranes was analyzed using time-of-flight secondary ion mass spectrometry (ToF-SIMS). The effects of different clinical cytotoxic agents were examined, including oxaliplatin, 5-fluorouracil and paclitaxel.
Our results indicate that chemotherapy affects the state of the plasma membrane irrespective of the mechanism of the drug action. For example, oxaliplatin induces increase of microviscosity of membrane, while paclitaxel decreases it. In both cases, the changes are associated with alterations in lipid composition [3, 4]. The acquisition of chemoresistance was accompanied by modification of membrane lipids in ways that preserve the viscous properties unchanged upon further treatment.
Therefore, we conclude that the ability of cancer cells to tightly control microviscosity of the plasma membrane and maintain it at a constant level is crucial for cell survival upon chemotherapeutic interventions.
The study was supported by the Russian Science Foundation (Project No. 20-14-00111, continuation).
[1] L. Shimolina et al. Imaging tumor microscopic viscosity in vivo using molecular rotors. Sci Rep. 41097, (2017)
[2] L. Shimolina et al. Probing Metabolism and Viscosity of Cancer Cells using Fluorescence Lifetime Imaging Microscopy. J. Vis. Exp. 173 e62708, (2021)
[3] L. Shimolina et al. The Role of Plasma Membrane Viscosity in the Response and Resistance of Cancer Cells to Oxaliplatin. Cancers, 13, 6165, 2021
[4] L. Shimolina et al Development of resistance to 5-fluorouracil affects membrane viscosity and lipid composition of cancer cells Methods Appl. Fluoresc. 10 044008, (2022)
