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Le Rôle de la myéline dans les maladies dégénératives

Abstract : The myelin sheath is essential for efficient electrical conduction of nerve impulses in the central and in the peripheral nervous system. To gain insight into the role of myelin, in autoimmune diseases that affect the nervous system, the influence of the myelin protein MBP-C1, a mutated form MBP-C8, and P2 on the membrane structure was investigated using neutron diffraction and on the membrane dynamics using incoherent elastic (EINS) and quasielastic neutron scattering (QENS). The experiments revealed that structural changes occur in the model myelin membranes across the temperature region covering the lipid phase transitions. The myelin proteins MBP-C1 and P2 are shown to strongly affect the structure of the model myelin membranes, shown by neutron diffraction measurements revealing significant changes in the bilayer spacing in the liquid phase. A range of distinct dynamical behaviours are observed by EINS in the model myelin membranes as a function of temperature: a first transition from a harmonic to an anharmonic temperature regime, assigned to methyl group rotations, is followed by further transitions induced by the gel-liquid phase transition of the bilayer and melting of the hydration water. MBP-C1 is shown to reduce the dynamics of the membrane, increasing the temperature at which the first transition occurs, and reducing the dynamics in the gel phase. These results were in agreement with quasielastic neutron scattering measurements, which showed a reduction of confined diffusive motions of the membrane in the gel phase induced by MBP-C1. In contrast, in the liquid phase, MBP-C1 was found to enhance diffusive motions, revealed with QENS, which is consistent with the observed changes to the bilayer structure that are induced by MBP-C1 in the liquid phase: due to the widening of the interbilayer space caused by MBP-C1, which penetrates into the bilayer, the lipids may have increased their conformational freedom. Any significant difference between the effects of MBP-C1 and its modified form MBP-C8, which is associated with multiple sclerosis, on motions of the membrane, investigated by QENS, were not identified in this study. It was demonstrated that both proteins MBP-C1 and P2 act in a highly synergistic manner and may associate within the membrane. Their ability to reduce the membrane dynamics in the liquid phase is considerably enhanced when both proteins are present. A model is proposed in which the associated proteins influence large fractions of the membranes by promoting adhesion between the bilayers through their strong electrostatic interactions and by their synergistic stacking effect.
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Submitted on : Tuesday, October 23, 2012 - 11:17:11 AM
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Wiebke Knoll. Le Rôle de la myéline dans les maladies dégénératives. Autre [cond-mat.other]. Université de Grenoble, 2012. Français. ⟨NNT : 2012GRENY030⟩. ⟨tel-00744455⟩

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