The aim of this paper is to present a new model of in vitro cell electropermeabilization, which describes separately the conducting state and the permeable state of the membrane submitted to high voltage pulses. We first derive the model based on the experimental observations and we present the numerical methods to solve the non-linear partial differential equations. We then present numerical simulations that corroborate qualitatively the experimental data dealing with the uptake of propidium iodide (PI) after millipulses. This tends to justify the validity of our modeling. Forthcoming work will be to calibrate the parameters of the model for quantitative description of the uptake.

Tumor growth curves are classically modeled by means of ordinary differential equations. In analyzing the Gompertz model several studies have reported a striking correlation between the two parameters of the model, which could be used to reduce the dimensionality and improve predictive power. We analyzed tumor growth kinetics within the statistical framework of nonlinear mixed-effects (population approach). This allowed the simultaneous modeling of tumor dynamics and inter-animal variability. Experimental data comprised three animal models of breast and lung cancers, with 833 measurements in 94 animals. Candidate models of tumor growth included the exponential, logistic and Gompertz models. The exponential and-more notably-logistic models failed to describe the experimental data whereas the Gompertz model generated very good fits. The previously reported populationlevel correlation between the Gompertz parameters was further confirmed in our analysis (R 2 > 0.92 in all groups). Combining this structural correlation with rigorous population parameter estimation, we propose a reduced Gompertz function consisting of a single individual parameter (and one population parameter). Leveraging the population approach using Bayesian inference, we estimated times of tumor initiation using three late measurement timepoints. The reduced Gompertz model was found to exhibit the best results, with drastic improvements when using Bayesian inference as compared to likelihood maximization alone, for both accuracy and precision. Specifically, mean accuracy (prediction error) was 12.2% versus 78% and mean precision (width of the 95% prediction interval) was 15.6 days versus 210 days, for the breast cancer cell line. These results demonstrate the superior predictive power of the reduced Gompertz model, especially when combined with Bayesian estimation. They offer possible clinical perspectives for personalized prediction of

The aim of this paper is to provide new models of cell electropermeabilization involving only a few parameters. A static and a dynamical model, which are based on the description of the electric potential in a biological cell, are derived. Existence and uniqueness results are provided for each differential system, and an accurate numerical method to compute the solution is described. We then present numerical simulations that corroborate the experimental observations, providing the consistency of the modeling. We emphasize that our new models involve very few parameters, compared with the most achieved models of Neu and Krassowska (Phys Rev E 53(3):3471-3482, 1999) and DeBruin and Krassowska (Biophys J 77:1225-1233, 1999), but they provide the same qualitative results. Thus, these models will facilitate drastically the forthcoming inverse problem solving, which will consist in fitting them with the experiments.

The impact of external medium conductivity on the efficiency of the reversible permeabilisation caused by pulsed electric fields was investigated. Pulses of 12 ns, 102 ns or 100 μs were investigated. Whenever permeabilisation could be detected after the delivery of one single pulse, media of lower conductivity induced more efficient reversible permeabilisation and thus independently of the medium composition. Effect of medium conductivity can however be hidden by some saturation effects, for example when pulses are cumulated (use of trains of 8 pulses) or when the detection method is not sensitive enough. This explains the contradicting results that can be found in the literature. The new data are complementary to those of one of our previous study in which an opposite effect of the conductivity was highlighted. It stresses that the conductivity of the medium influences the reversible permeabilization by several ways. Moreover, these results clearly indicate that electropermeabilisation does not linearly depend on the energy delivered to the cells.

International audienceWe study the behavior of the electro-quasistatic voltage potentials in a material composed by a bidimensional medium surrounded by a weakly oscillating thin layer and embedded in an ambient medium. We build approximate transmission conditions in order to replace the layer by these conditions on the boundary of the interior material. We deal with a weakly oscillating thin layer: the period of the oscillations is greater than the square root of the thinness. Our approach is essentially geometric and based on a suitable change of variable in the layer. This paper extends previous works of the former author, in which the layer had constant thickness

Abstract:We study the behavior of the steady-state voltage potentials in a material composed by a bidimensional medium surrounded by a rough thin layer and embedded in an ambient medium. The roughness of the layer is supposed to be ε-periodic, ε beeing the small thickness of the layer. We build approximate transmission conditions in order to replace the rough thin layer by these conditions on the boundary of the interior material. This paper extends previous works [8,7] of the third author, in which the layer had constant or weakly oscillating thickness.

Background. Since several decades, the experiments have highlighted the analogy of fusing cell aggregates with liquid droplets. The physical macroscopic models have been derived under incompressible assumptions. The aim of this paper is to provide a 3D model of growing spheroids, which is more relevant regarding embryo cell aggregates or tumor cell spheroids.Methods. We extend the past approach to a compressible 3D framework in order to account for the tumor spheroid growth. We exhibit the crucial importance of the effective surface tension, and of the inner pressure of the spheroid to describe precisely the fusion. The experimental data were obtained on spheroids of colon carcinoma human cells (HCT116 cell line). After 3 or 6 days of culture, two identical spheroids were transferred in one well and their fusion was monitored by live videomicroscopy acquisition each 2hours during 72h. From these images the neck radius and the diameter of the assembly of the fusing spheroids are extracted.Results. The numerical model is fitted with the experiments. It is worth noting that the time evolution of both neck radius and spheroid diameter are quantitatively obtained. The interesting feature lies in the fact that such measurements characterise the macroscopic rheological properties of the tumor spheroids. * guillaume.dechriste@gmail.com † jerome.fehrenbach@math.univ-toulouse.fr ‡ elena.griseti@ipbs.fr § Valerie.lobjois@itav.fr ¶ Corresponding author, clair.poignard@inria.fr 1 Conclusions. The experimental determination of the kinetics of neck radius and overall diameter during spheroids fusion characterises the rheological properties of the spheroids. The consistency of the model is shown by fitting the model with two different experiments, enhancing the importance of both surface tension and cell proliferation.General Significance. The paper sheds new light on the macroscopic rheological properties of tumor spheroids. It emphasizes the role of the surface tension and the inner pressure in the fusion of growing spheroid. Under geometrical assumptions, the model reduces to a 2-parameter differential equation fit with experimental measurements. The 3-D partial differential system makes it possible to study the fusion of spheroids in non-symmetrical or more general frameworks.

ABSTRACT. We present a review on the accuracy of asymptotic models for the scattering problem of electromagnetic waves in domains with thin layer. These models appear as first order approximations of the electromagnetic field. They are obtained thanks to a multiscale expansion of the exact solution with respect to the thickness of the thin layer, that makes possible to replace the thin layer by approximate conditions. We present the advantages and the drawbacks of several approximations together with numerical validations and simulations. The main motivation of this work concerns the computation of electromagnetic field in biological cells. The main difficulty to compute the local electric field lies in the thinness of the membrane and in the high contrast between the electrical conductivities of the cytoplasm and of the membrane, which provides a specific behavior of the electromagnetic field at low frequencies.