Changes in vesicle morphology induced by lateral phase separation modulate phospholipase A2 activity

Area of Science:

• Biochemistry
• Membrane Biophysics
• Enzymology

Background:

• Phospholipase A2 (PLA2) enzyme activity is influenced by lipid bilayer composition.
• Lateral phase separation of substrates and products can modulate PLA2 action.
• The precise mechanism linking phase separation to altered PLA2 activity remains unclear.

Purpose of the Study:

• To elucidate the mechanism by which lateral phase separation modulates phospholipase A2 activity.
• To investigate PLA2 activity in model lipid systems exhibiting controlled phase separation.
• To understand how structural changes in lipid bilayers affect enzyme kinetics.

Main Methods:

• Utilized two model lipid systems to study PLA2 activity.
• Induced lateral phase separation either a priori or in situ via PLA2 action.
• Analyzed changes in vesicle structure and catalytic rates.

Main Results:

• PLA2 exhibits higher activity in lipid dispersions with lateral phase separation.
• Lipid dispersions with pre-existing phase separation formed non-canonical structures (disk micelles/vesicles).
• In situ phase separation induced by PLA2 caused abrupt structural changes and a significant increase in catalytic rate.

Conclusions:

• Lateral phase separation significantly enhances PLA2 catalytic activity.
• The modulation of PLA2 activity is linked to alterations in membrane curvature and/or structural defects.
• Findings challenge previous assumptions about vesicle integrity during lipid hydrolysis.