Role of lipid composition on the structural and mechanical features of axonal membranes: a molecular simulation study

The integrity of cellular membranes is critical for the functionality of axons. Failure of the axonal membranes (plasma membrane and/or myelin sheath) can be the origin of neurological diseases. The two membranes differ in the content of sphingomyelin and galactosylceramide lipids. We investigate the relation between lipid content and bilayer structural-mechanical properties, to better understand the dependency of membrane properties on lipid composition. A sphingomyelin/phospholipid/cholesterol bilayer is used to mimic a plasma membrane and a galactosylceramide/phospholipid/cholesterol bilayer to mimic a myelin sheath. Molecular dynamics simulations are performed at atomistic and coarse-grained levels to characterize the bilayers at equilibrium and under deformation. For comparison, simulations of phospholipid and phospholipid/cholesterol bilayers are also performed. The results clearly show that the bilayer biomechanical and structural features depend on the lipid composition, independent of the molecular models. Both galactosylceramide or sphingomyelin lipids increase the order of aliphatic tails and resistance to water penetration. Having 30% galactosylceramide increases the bilayers stiffness. Galactosylceramide lipids pack together via sugar-sugar interactions and hydrogen-bond phosphocholine with a correlated increase of bilayer thickness. Our findings provide a molecular insight on role of lipid content in natural membranes.