Math. Model. Nat. Phenom.
Volume 15, 2020
|Number of page(s)||26|
|Published online||03 December 2020|
Microtubules (MT) a key target in oncology: mathematical modeling of anti-MT agents on cell migration
Aix Marseille Univ, CNRS Centrale Marseille, I2M and CNRS, INP, Inst Neurophysiopathol, Faculté de Pharmacie de Marseille,
2 Aix Marseille Univ, CNRS, INP, Inst Neurophysiopathol, Faculté de Pharmacie de Marseille, UMR 7051, 13385 Marseille, France.
3 Service pharmacie, CHU Hôpital de La Timone, APHM, Marseille, France.
4 Aix Marseille Univ, CNRS, Centrale Marseille, I2M, UMR 7373, 13453 Marseille, France.
5 Centre de mathématiques et de leurs applications, CNRS, ENS Paris-Saclay, Université Paris-Saclay, 94235 Cachan cedex, France.
* Corresponding author: email@example.com
Accepted: 27 February 2020
Microtubules (MTs) are protein filaments found in all eukaryotic cells which are crucial for many cellular processes including cell movement, cell differentiation, and cell division, making them a key target for anti-cancer treatment. In particular, it has been shown that at low dose, MT targeted agents (MTAs) may induce an anti-migratory effect on cancer and endothelial cells, leading to new prospects in cancer therapy. In that context, we propose to better understand the role of MT dynamics and thus of MTAs on cell migration using a mathematical cell centered model of cell migration taking into account the action of microtubules in the process. The model use a fluid based approach that describes, through level-set techniques, the deformation of the membrane during cell migration. The fluid part of the model is mainly composed of Stokes equations and the biochemical state of the cell is described using Reaction-Diffusion equations. Microtubules act on the biochemical state by activating or inactivating proteins of the Rho-GTPases family. The numerical simulation of the model is performed using Discrete Duality Finite Volume techniques. We describe the different schemes used for the simulation, focusing on the adaptation of preexisting methods to our particular case. Numerical simulation are performed, showing a realistic behavior of the simulated cells in term of shape, speed and microtubules dynamics. Different strategies for a depolymerizing MTA (Vincristin) mechanisms are investigated and show the robutness of our model.
Mathematics Subject Classification: 35Q92 / 92C37 / 65M08
Key words: Weighted essentially non-oscillatory / transport equation / discrete duality finite volume scheme
© The authors. Published by EDP Sciences, 2020
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Current usage metrics show cumulative count of Article Views (full-text article views including HTML views, PDF and ePub downloads, according to the available data) and Abstracts Views on Vision4Press platform.
Data correspond to usage on the plateform after 2015. The current usage metrics is available 48-96 hours after online publication and is updated daily on week days.
Initial download of the metrics may take a while.