Abstract
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.
Highlights
Axons are long projections of the nerve cell that are characterized by an excitable plasma membrane
No major difference in area per lipid is observed for SM-rich and GalCer-rich, except for coarse grained (CG) (42 nm) where a slighly lower value is observed in the presence of GalCer
The presence of cholesterol decreases the area per lipid of 21% and slightly increases the membrane thickness of around 7% in agreement with the nuclear magnetic resonance (NMR) data[53]
Summary
Axons are long projections of the nerve cell that are characterized by an excitable plasma membrane. The exposure to excessive stress can cause damage of the cellular membrane or myelin sheath, resulting in axon’s dysfunctions that can be the origin of neurological diseases[2,3,4] Knowing how these cellular elements respond to deformation is necessary to better understand their role in the axon. AFM experiments showed that cholesterol and sphingolipids enhance the mechanical resistance of lipid bilayers[18] These techniques have micron scale resolution and limitations: optical imaging limits micropipette aspiration, tip size and temperature dependence limit AFM. This results in large variation of reported values for mechanical stiffness of membranes and cells[19] and makes systematic comparison of lipid bilayers very difficult. Shigematsu et al.[27] studied the mechanical rupture of phospholipid bilayers containing different concentrations of cholesterol and showed that the critical strain for pore formation increases when the cholesterol concentration is 40%
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