An Unexpected Driving Force for Lipid Order Appears in Asymmetric Lipid Bilayers

Area of Science:

• Biophysics
• Membrane Biophysics
• Lipid Bilayer Dynamics

Background:

• Asymmetric lipid bilayers exhibit complex phase behavior.
• Cholesterol influences lipid ordering and phase separation.
• Understanding molecular mechanisms of lipid ordering is crucial.

Purpose of the Study:

• To investigate the molecular mechanism of induced order domain formation in asymmetric lipid bilayers.
• To explore how cholesterol redistribution drives lipid phase separation.
• To elucidate the energetic basis for precise domain superposition.

Main Methods:

• Utilizing dye partitioning to identify and label coexisting lipid phases (liquid-disordered, liquid-ordered, gel-ordered).
• Analyzing lipid compositions, specifically dioleoylphosphatidylcholine/cholesterol (DOPC/chol), to observe phase transitions.
• Investigating molecular-level interactions and redistribution of components within leaflets.

Main Results:

• An ordered phase in one leaflet precisely induces a superimposed ordered domain in the apposed leaflet.
• Cholesterol redistribution was observed in regions adjacent to ordered phases in a disordered lipid mixture (DOPC/chol = 0.8/0.2).
• Dye partitioning successfully labeled induced order domains and surrounding disordered lipid states.

Conclusions:

• The precise superposition of induced order domains suggests a significant energy penalty for order/disorder interfaces at the bilayer midplane.
• This energy penalty is sufficient to drive disordered lipid mixtures into an ordered state, minimizing unfavorable midplane contacts.
• Cholesterol plays a key role in mediating this induced ordering and phase separation phenomenon.