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 togetherviasugar-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.

Recognition between sperm and the egg surface marks the beginning of life in all sexually reproducing organisms. This fundamental biological event depends on the species-specific interaction between rapidly evolving counterpart molecules on the gametes. We report biochemical, crystallographic, and mutational studies of domain repeats 1-3 of invertebrate egg coat protein VERL and their interaction with cognate sperm protein lysin. VERL repeats fold like the functionally essential N-terminal repeat of mammalian sperm receptor ZP2, whose structure is also described here. Whereas sequence-divergent repeat 1 does not bind lysin, repeat 3 binds it non-species specifically via a high-affinity, largely hydrophobic interface. Due to its intermediate binding affinity, repeat 2 selectively interacts with lysin from the same species. Exposure of a highly positively charged surface of VERL-bound lysin suggests that complex formation both disrupts the organization of egg coat filaments and triggers their electrostatic repulsion, thereby opening a hole for sperm penetration and fusion.