Électroperméabilisation de systèmes modèles

Abstract : Electropermeabilization is a process based on the application of electric pulses which can induce a transient permeabilization of the cell plasma membrane. If you submit a cell to a sequence of electric pulses with appropriate amplitude and duration, you will manage to introduce in the cytoplasm some molecules otherwise unable to cross the external envelope, and to do so without decreasing cell viability. This technique has led to various applications, notably in the fight against cancer and in the field of gene therapy. Being safer than chemical and viral transfection methods, it has become increasingly popular among the medical community. However, membrane reorganization processes at the microscopic level are not yet fully understood, and are still a matter of debate. A better description of these phenomena would allow to improve the efficiency and the safety of the clinical protocols. In this prospect, a possible strategy consists in the study of electric field effects on model systems. This thesis focuses on the influence of long duration (in the millisecond range) electric pulses on artificial lipid systems, giant unilamellar vesicles. It explains how these studies on model systems contributed to our fundamental knowledge of electropermeabilization, and also how they resulted in two practical applications: a method for loading liposomes with macromolecules, and a method for measuring a characteristic physical property of lipid bilayers, the edge tension. It also contains a part where the entry of different molecules into electropermeabilized cells was studied via the numerical resolution of partial differential equations governing the evolution of the molecule concentration. This part of the thesis brings some clues for understanding the experimentally observed different behaviours between the electrotransfer of small and macromolecules.
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Biophysique [physics.bio-ph]. Université Paul Sabatier - Toulouse III, 2010. Français
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Submitted on : Saturday, October 23, 2010 - 2:23:43 PM
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Thomas Portet. Électroperméabilisation de systèmes modèles. Biophysique [physics.bio-ph]. Université Paul Sabatier - Toulouse III, 2010. Français. 〈tel-00528979〉



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