Utjecaj mijelinskog proteina na fazno stanje, morfologiju i strukturu membrane
Myelin is multibilayered, dominantly lipid sheath that enwraps axons and ensures proper transmission of neural impulses. One of the most highlighted compositional attributes of myelin is the domination of lipids (70-85 %) over proteins of which the most significant are proteolipid protein (PLP) and myelin basic protein (MBP) (15-30 %), with representative lipids being phospholipids (phosphatidylcholines (PCs), phosphatidylethanolamines (PEs), phosphatidylserines (PSs) and sphingomyelin (SM)) and cholesterol (chol). Disruption of spirally wrapped myelin sheath around axon axis is refferred as demyelination and it encompasses the effects such as the redundant unwrappping, vacuole formation and bilayer swelling due to water and ions leaking across the sheaths. Resulting with the impaired transmission of neural impulses, it produces clinical symptoms such as vision loss and muscle weakness which are common features of multiple sclerosis (MS). The studies of experimental autoimmune encephalomyelitis (EAE), as animal model of MS, demonstrated that the amount and ratios of representative myelin lipids were significantly modified in contrast with myelin of normal varieties and are further accompanied by reduced adhesive activity of myelin basic protein (MBP). Although extensively explored in vitro and in vivo models, a more detailed picture of the molecular level events that drive the demyelination in all of its forms remains unknown. This project aims to tackle these unknows by examination of model myelin membranes of different sizes and composition (with respect to the normal and modified myelin) in the presence of MBP and its simpler subunits (peptides) that make a direct interaction with lipid membrane. Model myelin membranes will be prepared as large and giant uni- and multilamellar liposomes (LUVs/GUVs and MLVs/GMVs) and their response to the presence of peptides and MBP will be analyzed with microscopic and spectroscopic techniques, as well with the support provided by molecular dynamics simulations. Aside of understanding demyelination at the molecular level, obtained results will help in suggesting possible solutions in lipid composition regulation either by medications and appropriate nutrition or will provide the guidelines towards building-up the artificial myelin structure.
DAAD-MZO bilateralna znanstveno-istraživačka suradnja
dr. sc. Rumiana Dimova, Max Planck Institute of Colloids and Interfaces, Potsdam, Njemačka