Which of the following phospholipids contributes to membrane fusion?
Stalk hypothesis posits fusion proceeds through negatively curved hourglass intermediate where proximal monolayers merge before distal creating hemifusion diaphragm. Conical lipids like phosphatidylethanolamine with small ethanolamine headgroup relatively large chain volume spontaneously adopt inverse hexagonal HII phase and stabilize stalk reducing bending energy dehydration cost from twenty to ten kBT. Sites exocytosis enrich PE via locally activated scramblases and PSD decarboxylase converting PS to PE within mitochondria and plasma membrane contact sites. Reconstituted vesicles containing thirty percent PE fuse tenfold faster with calcium or polyethylene glycol than pure PC vesicles measured by lipid mixing dequenching and content release assays. DAG and PA further promote due even smaller heads. Viral fusogens influenza hemagglutinin HIV gp41 insert amphipathic loops creating PE clustering lowering barrier. Sphingomyelin PC oppose fusion favoring lamellar phase. Understanding PE curvature promotion explains why synaptic vesicle membranes contain forty percent PE and why phospholipid shape targeted antimicrobial peptides defensins and why SNARE mediated release tightly coupled to lipid composition for efficient neurotransmission.
Ref: Chernomordik & Kozlov, Nature Struct Mol Biol 2008, PE and stalk fusion mechanism.