Hexagonal Substructure and Hydrogen Bonding in Liquid-Ordered Phases Containing Palmitoyl Sphingomyelin.

Area of Science:

• Biophysics
• Computational Chemistry
• Materials Science

Background:

• Cell membranes are complex mixtures of lipids and cholesterol.
• Understanding lipid-cholesterol interactions is crucial for cell membrane function.
• Sphingomyelin and phosphatidylcholine are key membrane components.

Purpose of the Study:

• To investigate cholesterol's interactions within ternary lipid mixtures.
• To compare cholesterol solvation and binding preferences in different lipid environments.
• To elucidate the specific role of hydrogen bonding between cholesterol and sphingomyelin.

Main Methods:

• All-atom molecular dynamics simulations were performed.
• Ternary mixtures of sphingomyelin, cholesterol, and phosphatidylcholine (POPC or DOPC) were simulated.
• Mixtures representing liquid-ordered, liquid-disordered, and coexisting phases were analyzed.

Main Results:

• Cholesterol preferentially solvates DOPC over POPC when both are present.
• In POPC-containing mixtures, cholesterol prefers solvation by PSM.
• Cholesterol interacts with DPPC via its smooth face and with PSM via its rough face.
• Cholesterol-PSM hydrogen bonding alters PSM amide tilt and enhances further PSM-PSM hydrogen bonding.
• This specific hydrogen bonding also modifies hydrocarbon chain packing in the liquid-ordered phase.

Conclusions:

• Cholesterol's solvation and interaction preferences are highly dependent on the specific phospholipid and sphingolipid composition.
• Unique hydrogen bonding interactions between cholesterol and PSM significantly influence local membrane structure and lipid packing.
• These findings provide detailed insights into the molecular mechanisms governing lipid raft formation and membrane heterogeneity.