Caractérisation des propriétés mécaniques de cellules adhérentes: Interprétation des mesures issues de la technique des pinces optiques

La caractérisation précise des propriétés mécaniques de cellules animales est cruciale pour comprendre et analyser comment celles-ci répondent à des stimuli mécaniques (mécanotransduction) in vivo. Parmi les différentes techniques expérimentales mises en oeuvre, la micromanipulation de microbilles par pinces optiques, déjà utilisée avec succès pour quantifier l'élasticité des globules rouges, a été appliquée aux mesures de rigidité de cellules adhérentes. Cependant, les rapports force externe imposée/translation de la bille issus des mesures expérimentales dépendent fortement des caractéristiques géométriques de l'interface bille-cellule et notamment de l'angle d'imprégnation de la microbille, de son rayon R et de l'épaisseur h de la cellule. En simulant par éléments finis la déformation d'une cellule adhérente par pinces optiques, nous avons pu établir des fonctions de correction qui permettent de remonter au module de Young intrinsèque du milieu cellulaire à partir du module d'élasticité apparent déterminé expérimentalement

Mathematical modelling of anisotropy in fibrous connective tissue

We present two modelling frameworks for studying dynamic anistropy in connective tissue, motivated by the problem of fibre alignment in wound healing. The first model is a system of partial differential equations operating on a macroscopic scale. We show that a model consisting of a single extracellular matrix material aligned by fibroblasts via flux and stress exhibits behaviour that is incompatible with experimental observations. We extend the model to two matrix types and show that the results of this extended model are robust and consistent with experiment. The second model represents cells as discrete objects in a continuum of ECM. We show that this model predicts patterns of alignment on macroscopic length scales that are lost in a continuum model of the cell population

Pattern Formation of Glioma Cells: Effects of Adhesion

We investigate clustering of malignant glioma cells. \emph{In vitro} experiments in collagen gels identified a cell line that formed clusters in a region of low cell density, whereas a very similar cell line (which lacks an important mutation) did not cluster significantly. We hypothesize that the mutation affects the strength of cell-cell adhesion. We investigate this effect in a new experiment, which follows the clustering dynamics of glioma cells on a surface. We interpret our results in terms of a stochastic model and identify two mechanisms of clustering. First, there is a critical value of the strength of adhesion; above the threshold, large clusters grow from a homogeneous suspension of cells; below it, the system remains homogeneous, similarly to the ordinary phase separation. Second, when cells form a cluster, we have evidence that they increase their proliferation rate. We have successfully reproduced the experimental findings and found that both mechanisms are crucial for cluster formation and growth.Comment: 6 pages, 6 figure

Caractérisation des propriétés mécaniques anisotropes de la paroi artérielle saine à partir de la méthode des champs virtuels

Dans ce travail, nous appliquons la théorie des champs virtuels développée par Grediac et al. (2002) à l'étude de la caractérisation des propriétés mécaniques isotropes transverses de la paroi artérielle saine. Nos résultats montrent que cette approche reste prometteuse malgré une sensibilité au bruit non négligeable lorsque l'on cherche à caractériser en particulier le module d'Young radial de la paroi vasculaire. Abstract : This work is an adaptation of the theory of virtual fields developed by Grediac et al. (2002) for the identification of the orthotropic mechanical properties of the arterial wall. From this method we successfully characterized the anisotropy of a healthy arterial wall. Nevertheless, the robustness of the algorithm towards noise and particular when the radial Young's modulus is investigated, seems limited

Multiscale modelling of vascular tumour growth in 3D: the roles of domain size & boundary condition

We investigate a three-dimensional multiscale model of vascular tumour growth, which couples blood flow, angiogenesis, vascular remodelling, nutrient/growth factor transport, movement of, and interactions between, normal and tumour cells, and nutrient-dependent cell cycle dynamics within each cell. In particular, we determine how the domain size, aspect ratio and initial vascular network influence the tumour's growth dynamics and its long-time composition. We establish whether it is possible to extrapolate simulation results obtained for small domains to larger ones, by constructing a large simulation domain from a number of identical subdomains, each subsystem initially comprising two parallel parent vessels, with associated cells and diffusible substances. We find that the subsystem is not representative of the full domain and conclude that, for this initial vessel geometry, interactions between adjacent subsystems contribute to the overall growth dynamics. We then show that extrapolation of results from a small subdomain to a larger domain can only be made if the subdomain is sufficiently large and is initialised with a sufficiently complex vascular network. Motivated by these results, we perform simulations to investigate the tumour's response to therapy and show that the probability of tumour elimination in a larger domain can be extrapolated from simulation results on a smaller domain. Finally, we demonstrate how our model may be combined with experimental data, to predict the spatio-temporal evolution of a vascular tumour

Predicting the Location of Glioma Recurrence After a Resection Surgery

International audienceWe propose a method for estimating the location of glioma recurrence after surgical resection. This method consists of a pipeline including the registration of images at different time points, the estimation of the tumor infiltration map, and the prediction of tumor regrowth using a reaction-diffusion model. A data set acquired on a patient with a low-grade glioma and post surgery MRIs is considered to evaluate the accuracy of the estimated recurrence locations found using our method. We observed good agreement in tumor volume prediction and qualitative matching in regrowth locations. Therefore, the proposed method seems adequate for modeling low-grade glioma recurrence. This tool could help clinicians anticipate tumor regrowth and better characterize the radiologically non-visible infiltrative extent of the tumor. Such information could pave the way for model-based personalization of treatment planning in a near future

Suicide by Skull Stab Wounds: A Case of Drug-Induced Psychosis

Suicide by stabbing to the head and/or driving sharp objects into the skull is of extreme rarity. This article reports the case of a 27-year-old man, who committed suicide by multiple knife stabs and cuts to the head, the torso, one shoulder and the forearms. Autopsy showed a perforating wound of the skull and the 10-cm long broken blade of the knife being still embedded in the right temporal lobe of the brain. The deceased had no history of psychiatric illness but was currently treated by mefloquine, a quinine derivative associated with a high rate of psychiatric adverse effects. Toxicological examination confirmed a recent intake of mefloquine together with chloroquine, another antimalarial drug. To our knowledge, this is the first report of a completed suicide with very strong evidence of mefloquine implication. Discussion focuses upon mefloquine-induced psychiatric disorders and highlights the importance of performing toxicological investigations in cases of unusual suicides

The concentration of three anti-seizure medications in hair: the effects of hair color, controlling for dose and age

BACKGROUND: This paper assess the relationship between the quantity of three anti-seizure medications in hair and the color of the analyzed hair, while controlling for the effects of dose, dose duration, and patient age for 140 clinical patients undergoing anti-seizure therapy. Three drugs are assessed: carbamazepine (40 patients), valproic acid (40 patients), and phenytoin (60 patients). The relationship between hair assay results, hair color, dose, dose duration, and age is modeled using an analysis of covariance. The covariance model posits the hair assay results as the dependent variable, the hair color as the qualitative categorical independent variable, and dose, dose duration, and age as covariates. The null hypothesis assessed is that there is a no relationship between hair color and the quantity of analyte determined by hair assay such that darker colored hair will demonstrate higher concentrations of analyte than lighter colored hair. RESULTS: The analysis reveals that there is a significant relationship between dose and concentration for all hair color categories independent of the other covariates or the categorical independent variable. CONCLUSION: There does not appear to be any relationship between carbamazepine concentration and hair color. There is a weak relationship between hair color and valproic acid concentration, which the data suggest may be mediated by age. There is a significant, moderate relationship between phenytoin concentration and hair color such that darker colored hair has greater concentration values than lighter colored hair