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Autoassemblage des virus enveloppés : dynamique théorique et méthodes d'analyse des mesures par fluorescence

Abstract : In this thesis work, we study the self-assembly of viral particles and focus on the analysis of measurements based on fluorescence labeling of viral proteins. We propose a theoretical model of the dynamic of viral proteins self-assembly at the cell membrane based on previous models developed to describe the in-vitro assembly of spherical viruses. We study the evolution of the populations in the successive stages of viral budding as well as the evolution of single particle within this framework. We also provide various data analysis to measure the physical values involved in the process: rate of aggregation during the bud growth, size and shape of the eventual structure. Viruses are biological objects unable to replicate without infecting an host cell since they lack part of the molecular machinery mandatory for genetic code replication and proteins production. Originally aimed at controlling the diseases they cause, the study of viruses is now rich of applications in medical and technological field (gene therapy, phage therapy, targeted therapy, bio-templating, cargo specific encapsulation, etc.). The existent models describing the self-assembly of viral proteins have successfully captured many features observed in the in-vitro experiments. We study the expected evolution when an open system is considered with an input flux of proteins and an output flux of released virion, characteristic of the in-vivo situation. We derive the population distribution at steady state and numerically study their dynamic under constant viral protein input flux. We also study the case of a single bud evolution which can be followed by its fluorescence emission. We study the possibility to estimate shape parameters at the single viral particle level such as radius and completion for the human immunodeficiency virus (HIV) from single molecule localization superresolution microscopy. These techniques known as (f)PALM or (d)STORM, record labeled proteins position with a precision of few to tens of nanometers. We propose an approach base on the maximum likelihood statistical method which is tested on both real and simulated images of fully formed particles. Our results suggest that it can offer a precision on the determination of the global structure finner than the positioning precision of the single proteins. This efficiency is however tempered when the parameter of interest does not affect the figures of merit to which the method is sensitive such as the apparent area and the image contours
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Timothée Verdier. Autoassemblage des virus enveloppés : dynamique théorique et méthodes d'analyse des mesures par fluorescence. Physics [physics]. Université Claude Bernard - Lyon I, 2015. English. ⟨NNT : 2015LYO10226⟩. ⟨tel-01281377⟩

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