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From monomer to the cell: Models for actin dynamics

Identifieur interne : 000195 ( Hal/Checkpoint ); précédent : 000194; suivant : 000196

From monomer to the cell: Models for actin dynamics

Auteurs : Julien Berro [France]

Source :

RBID : Hal:tel-00221384

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English descriptors

Abstract

Actin filaments are biological polymers that are very abundant in eucaryot cytoskeleton. Their auto-assembly and auto-organization are highly dynamic and are essential in cell motility and membrane deformations. In this thesis we propose three approaches, on different scales, in order to enlighten mechanisms for the regulation of assembly of, organization of and production of force by biological filaments such as actin filaments. First, we have developed a stochastic multi-agent simulation tool for studying biological filaments taking into consideration interactions on the nanometer scale. This new tool allowed us to bring out the acceleration of actin monomer turnover due to fragmentation of filaments by ADF/Cofilin and the symmetry breaking induced by this protein, which agree well with experimental data from L. Blanchoin team (CEA Grenoble). Secondly, we studied a continuous model for filament buckling, providing, on the one hand, an estimation of forces exerted in vitro or in vivo with respect to extremity attachment conditions and, on the other hand, limit conditions for buckling. Thirdly, we developed a framework for organizing kinetic biochemical data from reaction networks, which was used for the regulation of actin polymerization. These three modeling approaches improved the knowledge on actin dynamics and are useful complements for experimental approaches in biology.

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Hal:tel-00221384

Le document en format XML

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<abstract xml:lang="fr">Les filaments d'actine sont des polymères biologiques très abondants dans le cytosquelette des eucaryotes. Leur auto-assemblage et leur auto-organisation sont très dynamiques et ils jouent un rôle majeur dans la motilité cellulaire et dans les déformations de la membrane. Nous présentons dans cette thèse trois approches de modélisation, à différentes échelles, afin de mieux comprendre les mécanismes de régulation de l'assemblage, de l'organisation et de la production de forces par des filaments biologiques tels que les filaments d'actine. Nous avons tout d'abord développé un outil de simulation multi-agent stochastique pour l'étude de la dynamique de filaments biologiques prenant en compte les interactions à l'échelle du nanomètre. Ce nouvel outil nous a permis de mettre en évidence l'accélération du turnover des monomères d'actine par fragmentation des filaments par l'ADF/Cofiline ainsi que les ruptures de symétries induites par cette protéine, résultats concordant avec les expériences de l'équipe de L. Blanchoin (CEA Grenoble). Nous avons également mené l'étude d'un modèle continu pour le flambage de filaments qui a permis d'estimer les forces exercées in vivo et in vitro en fonction des conditions d'attachement des extrémités et de donner des conditions limites de certains paramètres permettant le flambage. Troisièmement, nous avons développé un cadre pour l'organisation des données de cinétique biochimique de réseaux de régulation que nous avons utilisé pour la régulation de la polymérisation de l'actine. Ces trois approches de modélisation ont permis d'améliorer la connaissance sur la dynamique de l'actine et sont complémentaires aux approches expérimentales de la biologie.</abstract>
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