Biophysical modeling of anti-cancerous therapies: project MEMOVE 

Participants: Clair Poignard, Michaël Leguèbe.

Partners:
Team of Vectorology and Anticancer Therapies at the Institut Gustave Roussy (VAT lab), Villejuif
Department of Mathematics of the University of Versailles (LMV)
Bioengineering laboratory Ampère, Lyon

MEMOVE (Multiscale Electroporation MOdeling Validated by the Experiments) is a transdisciplinary project that aims at developing new mathematical models, numerical tools as well as new experimental protocols to provide a complete understanding of the electropermeabilization from the cell to the tissue scale. The electroporation modeling will be developed thanks to two-way links between the numerical simulations and the experiments: the experimental results providing preliminary results to the modeling, which then will highlight a priori the main phenomena of the experiments. The fitting of the model based on PDEs is the key point of the project. This will be performed by a data assimilation procedure well known by the INRIA team MC2.
At the cell scale, it is proposed to develop new electrical cell PDEs models that describe simultaneously the electropermeabilization by micropulses, and the electrophysiological changes of the cell during the process (cell swelling, ions fluxes in the cell...). Moreover a theoretical asymptotic analysis will be performed to study the electropermeabilization of closely touching cells, while homogenization of single cell models will help in the understanding of the electroporation of cell suspension solution. From the experimental point of view, new device manufacturing to simultaneously electroporate vesicles and quantify this electroporation will be performed. These experiments will highlight the specificity of cell electroporation, when compared to the simplest experimental cell model that is liposome.
At the tissue scale, MEMOVE aims at providing a non-linear tissue conductivity modeling, with parameters that will be fitted with the experiments on potatoes, and rat liver, through data assimilation techniques based on proper orthogonal decomposition developed by MC2. Here again, both numerical and experimental influences of the pulse properties on the tissue electroporation will be investigated.
The final goal of the project, once these multiscale models will be derived, is to provide numerical tools that ensure the optimal pulse delivery for a given realistic geometry of tissue, in order to propose a code that could be useful to the physician applying electrochemotherapy as cancer treatment. The full human body meshing developed by Ampère will be useful to perform the robust optimization to ensure the best pulse delivery that will be addressed by Ampère, MC2 and LMV. The results will be proposed to the VAT lab to test the procedure on the electroporation on small animals and to evaluate the consistence of the optimization.

O. Kavian, M. Leguèbe, C. Poignard, L. Weynans. Classical electropermeabilization modelling at the cell scale. Accepted in Journal of Mathematical Biology.

Extra- and intra-cellular electric field, with poration in blue areas and holes of the cellular membrane.