Structure of Sphingomyelin Bilayers: A Simulation Study

Abstract

We have carried out a molecular dynamics simulation of a hydrated 18:0 sphingomyelin lipid bilayer. The bilayer contained 1600 sphingomyelin (SM) molecules, and 50,592 water molecules. After construction and initial equilibration, the simulation was run for 3.8 ns at a constant temperature of 50 degrees C and a constant pressure of 1 atm. We present properties of the bilayer calculated from the simulation, and compare with experimental data and with properties of dipalmitoyl phosphatidylcholine (DPPC) bilayers. The SM bilayers are significantly more ordered and compact than DPPC bilayers at the same temperature. SM bilayers also exhibit significant intramolecular hydrogen bonding between phosphate ester oxygen and hydroxyl hydrogen atoms. This results in a decreased hydration in the polar region of the SM bilayer compared with DPPC. Since our simulation system is very large we have calculated the power spectrum of bilayer undulation and peristaltic modes, and we compare these data with similar calculations for DPPC bilayers. We find that the SM bilayer has significantly larger bending modulus and area compressibility compared to DPPC.

Tales and Mysteries of the Enigmatic Sphingomyelin Synthase Family

“…[49][50][51][52][53] Recent evidence has further enriched this model supporting a role for SM in the homeostasis of lipid microdomains at the plasma membrane, often sites of receptor-mediated signaling. Taking advantage of the identification of SMS1 as bona fide SM synthase, the role of SM in the activation of Fas signaling was investigated by Miyaji et al 75 Comparing SMS1 deficient cells (with over expressed Fas receptor) with cells in which expression of SMS1 was restored, the authors provide evidence for a critical role of SM in Fas-mediated signaling by enabling the formation of the death-inducing signaling complex (DISC) and consequently allowing caspase activation and production of ceramide at the plasma membrane.…”

“…In fact, the predominant presence of saturated fatty acids and the potential intermolecular hydrogen binding, via the amide bond and the free hydroxyl group at position 3, favor a high-density packing of SM, which increases the compactness and impermeability of the membrane. [51][52][53] According to the umbrella model, 54 the preferential mixing of sterols with SM is caused by shielding of the nonpolar sterol molecule by the phosphocholine head group of SM. Collectively these physicochemical features are believed to influence the lateral organization of cellular membranes.…”

Use of fluorescence to determine the effects of cholesterol on lipid behavior in sphingomyelin liposomes and erythrocyte membranes

“…Inferences from previous molecular simulations of sphingomyelin model membranes may explain these observations. Those simulations revealed additional intramolecular and intermolecular hydrogen bonding established by the nitrogen group of sphingomyelin that would not be possible for phosphatidylcholine (44,45). These hydrogen bonds among sphingomyelin molecules are likely to restrict partitioning of prodan and nystatin while limiting MC540 to adsorption superficial to the bonds.…”

Coarse-grained model for phospholipid/cholesterol bilayer

“…The duration of such a simulation is typically limited to about 100 ns. A few more ambitious MD simulations on systems with a larger number of molecules have been reported, 14,15,16 but the sizes are still rather modest: the largest MD studies of lipid bilayers contain of the order of 10 3 lipid molecules. The time scales reached in such simulations are currently only tens of nanoseconds.…”