Molecular Dynamics Simulations Reveal Leaflet Coupling in Compositionally Asymmetric Phase-Separated Lipid Membranes

Area of Science:

• Biophysics
• Cell Biology
• Biochemistry

Background:

• Eukaryotic plasma membranes exhibit asymmetric lipid distribution.
• Liquid-ordered (Lo) and liquid-disordered (Ld) domains form via phase separation in the exoplasmic leaflet.
• The coupling mechanism between exoplasmic and cytoplasmic leaflets remains unclear.

Purpose of the Study:

• Investigate leaflet coupling in asymmetric lipid bilayers.
• Understand how exoplasmic leaflet phase separation influences the cytoplasmic leaflet.
• Determine if information is communicated across the membrane.

Main Methods:

• All-atom molecular dynamics simulations.
• Modeling compositionally asymmetric lipid bilayers.
• Analyzing lipid ordering, thickness, and composition.

Main Results:

• The cytoplasmic leaflet region opposing the exoplasmic Lo domain showed increased order and thickness.
• This opposing region was enriched in cholesterol and depleted of polyunsaturated lipids.
• Phase separation in one leaflet influences the properties of the apposing leaflet.

Conclusions:

• Demonstrates cross-leaflet communication in asymmetric lipid bilayers.
• Suggests a mechanism for how exoplasmic raft domains affect the cytoplasmic leaflet.
• Provides insights into plasma membrane organization and function.