Two Coexisting Membrane Structures Are Defined by Lateral and Transbilayer Interactions between Sphingomyelin and...

Area of Science:

• Membrane biophysics
• Lipid bilayer structure
• Molecular dynamics simulations

Background:

• Sphingomyelin and cholesterol are key membrane components.
• Understanding their interactions is crucial for membrane function.
• Cholesterol's role in lipid rafts and membrane fluidity is well-established.

Purpose of the Study:

• To elucidate the structural organization of palmitoylsphingomyelin (PSM) and cholesterol bilayers.
• To investigate the molecular mechanisms of cholesterol-phospholipid interactions.
• To explore the role of phospholipid asymmetry in these interactions.

Main Methods:

• Synchrotron X-ray powder diffraction to determine bilayer structure.
• Atomistic molecular dynamics (MD) simulations for molecular-level insights.
• Unsupervised clustering of interatomic distances to analyze interactions.

Main Results:

• Two coexisting bilayer structures of PSM-cholesterol were identified.
• PSM asymmetry was found to be critical for driving cholesterol interactions.
• Four distinct interaction modes were observed, including cholesterol dehydration mechanisms.
• Specific interactions involving the N-acylated fatty acid of PSM were identified.

Conclusions:

• Cholesterol's preferential interaction with sphingomyelin over glycerophospholipids is explained by specific PSM interactions.
• The study provides mechanistic insights into the 'umbrella model' of cholesterol hydration.
• Phospholipid asymmetry is a key factor governing cholesterol's behavior in lipid bilayers.