Contributions à la modélisation mathématique et numérique de problèmes issus de la biologie - Applications aux Prions et à la maladie d'Alzheimer

Erwan Hingant 1, 2
2 DRACULA - Multi-scale modelling of cell dynamics : application to hematopoiesis
ICJ - Institut Camille Jordan [Villeurbanne], Inria Grenoble - Rhône-Alpes, CGPhiMC - Centre de génétique et de physiologie moléculaire et cellulaire
Abstract : The aim of this thesis is to study, under several aspects, the formation of amyloids from proteins polymerization. The mathematical modelling of these phenomena in the case of in vitro or in vivo polymerisation remains questioned. We then propose here several models, which are also investigated from theoritical and numerical point of view. In the first part we present works done in collaboration with biologists. We propose two models based on the current theory on Prion phenomena that are designed for specific experimental conditions. These models allow us to analyse the experimental data obtained in laboratory and raise phenomena that remain unexplained by the theory. Then, from these results and biophysical considerations, we introduce a model which corroborates with data and provides a new approach on the amyloid formation in the particular case of Prion. This part is ended by the mathematical analysis of the model consisting of an infinite set of differentials equations. The system analysed is a Becker-Döring system coupled to a discrete growth-fragmentation system. The second part is dedicated to the analysis of a new model for polymerization of proteins with fragmentation subject to the surrounding variations of the fluid. Thus, we propose a model which is close to the experimental conditions and introduce new measur- able macroscopic quantities to study the polymerization. The first introductory chapter states the stochastic description of the problem. We give the equations of motion for each polymers and monomers as well as a general formalism to study the limit in large number. Next, we give the mathematical framework and prove the existence of solutions to the Fokker-Planck-Smoluchowski equation for the configurational density of polymers coupled to the diffusion equation for monomers. The last chapter provides a numerical method adapted to this problem with numerical simulations In the last part, we are interested in modelling Alzheimer's disease. We introduce a model that describes the formation of amyloids plaques in the brain and the interactions between Aβ-oligomers and Prion proteins which might be responsible of the memory impairment. We carry out the mathematical analysis of the model. Namely, for a constant polymerization rate, we provide existence and uniqueness together with stability of the equilibrium. Finally we study the existence in a more general and biological relevant case, that is when the polymerization depends on the size of the amyloid.
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Erwan Hingant. Contributions à la modélisation mathématique et numérique de problèmes issus de la biologie - Applications aux Prions et à la maladie d'Alzheimer. Equations aux dérivées partielles [math.AP]. Université Claude Bernard - Lyon I, 2012. Français. ⟨tel-00763444⟩

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