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

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

Modelling of complex biological systems in the context of genomics: an account of a multidisciplinary thematic seminar held in Montpellier (France) in April 2005

International audienceno abstrac

Robustness Analysis and Behavior Discrimination in Enzymatic Reaction Networks

Characterizing the behavior and robustness of enzymatic networks with numerous variables and unknown parameter values is a major challenge in biology, especially when some enzymes have counter-intuitive properties or switch-like behavior between activation and inhibition. In this paper, we propose new methodological and tool-supported contributions, based on the intuitive formalism of temporal logic, to express in a rigorous manner arbitrarily complex dynamical properties. Our multi-step analysis allows efficient sampling of the parameter space in order to define feasible regions in which the model exhibits imposed or experimentally observed behaviors. In a first step, an algorithmic methodology involving sensitivity analysis is conducted to determine bifurcation thresholds for a limited number of model parameters or initial conditions. In a second step, this boundary detection is supplemented by a global robustness analysis, based on quasi-Monte Carlo approach that takes into account all model parameters. We apply this method to a well-documented enzymatic reaction network describing collagen proteolysis by matrix metalloproteinase MMP2 and membrane type 1 metalloproteinase (MT1-MMP) in the presence of tissue inhibitor of metalloproteinase TIMP2. For this model, our method provides an extended analysis and quantification of network robustness toward paradoxical TIMP2 switching activity between activation or inhibition of MMP2 production. Further implication of our approach is illustrated by demonstrating and analyzing the possible existence of oscillatory behaviors when considering an extended open configuration of the enzymatic network. Notably, we construct bifurcation diagrams that specify key parameters values controlling the co-existence of stable steady and non-steady oscillatory proteolytic dynamics

Des concepts de la dynamique non lineaire a l'auto-organisation des systemes biologiques: attracteurs multiples, structures de bifurcation et trajectoires spatio-temporelles d'un modele autocatalytique du metabolisme mineral osseux

SIGLEAvailable from INIST (FR), Document Supply Service, under shelf-number : TD 20292 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

Transmission of mechanical stresses within the cytoskeleton of adherent cells: a theoretical analysis based on a multi-component cell model.

International audienceHow environmental mechanical forces affect cellular functions is a central problem in cell biology. Theoretical models of cellular biomechanics provide relevant tools for understanding how the contributions of deformable intracellular components and specific adhesion conditions at the cell interface are integrated for determining the overall balance of mechanical forces within the cell. We investigate here the spatial distributions of intracellular stresses when adherent cells are probed by magnetic twisting cytometry. The influence of the cell nucleus stiffness on the simulated nonlinear torque-bead rotation response is analyzed by considering a finite element multi-component cell model in which the cell and its nucleus are considered as different hyperelastic materials. We additionally take into account the mechanical properties of the basal cell cortex, which can be affected by the interaction of the basal cell membrane with the extracellular substrate. In agreement with data obtained on epithelial cells, the simulated behaviour of the cell model relates the hyperelastic response observed at the entire cell scale to the distribution of stresses and strains within the nucleus and the cytoskeleton, up to cell adhesion areas. These results, which indicate how mechanical forces are transmitted at distant points through the cytoskeleton, are compared to recent data imaging the highly localized distribution of intracellular stresses

Migration de cellules virtuelles déformables : Modélisation biomécanique multi-agent de la migration cellulaire

National audienceWe present an integrative model for simulating the migration of deformable virtual cells over an anisotropic substrate exhibiting an adhesion gradient. We implemented an original multi-agent based model, which enables to analyse the influence of cell-substrate mechanical interactions on cell motility. The deformations and displacements of the cells are determined both by the adhesion forces that come into play during migration and by the recruitment of transmembrane receptors. In agreement with experimental data, we specifically showed that cell migration speed varies nonlinearly with substrate bonds concentration. We furthermore analysed the influence of different regulation mechanisms of receptors clustering onto increased cell motility

Migration de cellules virtuelles déformables : Modélisation biomécanique multi-agent de la migration cellulaire

National audienceWe present an integrative model for simulating the migration of deformable virtual cells over an anisotropic substrate exhibiting an adhesion gradient. We implemented an original multi-agent based model, which enables to analyse the influence of cell-substrate mechanical interactions on cell motility. The deformations and displacements of the cells are determined both by the adhesion forces that come into play during migration and by the recruitment of transmembrane receptors. In agreement with experimental data, we specifically showed that cell migration speed varies nonlinearly with substrate bonds concentration. We furthermore analysed the influence of different regulation mechanisms of receptors clustering onto increased cell motility