Liquid-ordered lipid domains, also called rafts, are assumed to be important players in different cellular processes, mainly signal transduction and membrane trafficking. They are thicker than the disordered part of the membrane and are thought to form to compensate for the hydrophobic mismatch between transmembrane proteins and the lipid environment. Despite the existence of such structures in vivo still being an open question, they are observed in model systems of multicomponent lipid bilayers. Moreover, the predictions obtained from model experiments allow the explanation of different physiological processes possibly involving rafts. Here we present the results of the study of the regulation of raft size distribution by ganglioside GM1. Combining atomic force microscopy with theoretical considerations based on the theory of membrane elasticity, we predict that this glycolipid should change the line tension of raft boundaries in two different ways, mainly depending on the cholesterol content. These results explain the shedding of gangliosides from the surface of tumor cells and the following ganglioside-induced apoptosis of T-lymphocytes in a raft-dependent manner. Moreover, the generality of the model allows the prediction of the line activity of different membrane components based on their molecular geometry.
Cholesterol is known for its condensing effect on phospholipids, which was first discovered in monolayers (Leathes, 1925), i.e., a binary mixture of a phospholipid and cholesterol have an average molecular area less than the sum of the molecular areas of the two components. The corresponding effect in bilayers where the thickness of the mixture is greater than that of each component alone is also well-known (Levine and Wilkins, 1971). At the maximum solubility, cholesterol can increase the thickness of DOPC by 5.1 Å , SOPC by 5.8 Å ,
The myelin sheath is an insulating, compacted, multilamellar biological membrane that facilitates efficient propagation of action potentials down neuronal axons, and is critical for proper physiological function. Recently, EM imaging has provided compelling in vivo data that puts to question the long-established mechanism for the formation of central nervous system (CNS) myelin. The new data have led to the proposal of a new model involving (1) the preformation of myelin membrane tubules that are trafficked to the neuronal axon, where they (2) undergo a transition from tubular to lamellar form and thus form the final compact myelin sheath [Szuchet et al. J. Struct. Biol. 190, 56-72 (2015)]. To investigate this mechanism, we designed in vitro experiments to probe the interactions of myelin lipids as they (1) self-assemble into tubules and (2) transition into lamellar form. Using fluid-cell AFM, TEM, and DLS, we have investigated the self-assembly of lipidic tubules, their transition into the multilamellar structure of mature myelin, and how this process is modulated by lipid composition and the presence of myelin basic protein. Our data support a galactosylceramide (GalCer) concentration-dependent response in lipid morphology that drives a transition from stable tubules to nonspecific aggregates with decreasing GalCer concentration. Our in vitro findings at high GalCer concentrations align with the in vivo tubules observed in ovine embryonic oligodendrocytes, suggesting that these structures of major myelin lipids can be stable precursors for myelination.
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