Phospholipase A₂‑Induced Remodeling Processes on Liquid-Ordered/Liquid-Disordered Membranes Containing Docosahexaenoic or Oleic Acid: A Comparison Study

Vesicle cycling, which is an important biological event, involves the interplay between membrane lipids and proteins, among which the enzyme phospholipase A₂ (PLA₂) plays a critical role. The capacity of PLA₂ to trigger the budding and fission of liquid-ordered (L_o) domains has been examined in palmitoyl-docosahexaenoylphosphatidylcholine (PDPC) and palmitoyl-oleoylphosphatidylcholine (POPC)/sphingomyelin/cholesterol membranes. They both exhibited a L_o/liquid-disordered (L_d) phase separation. We demonstrated that PLA₂ was able to trigger budding in PDPC-containing vesicles but not POPC ones. The enzymatic activity, line tension, and elasticity of the membrane surrounding the L_o domains are critical for budding. The higher line tension of L_o domains in PDPC mixtures was assigned to the greater difference in order parameters of the coexisting phases. The higher amount of lysophosphatidylcholine generated by PLA₂ in the PDPC-containing mixtures led to a less-rigid membrane, compared to POPC. The more elastic L_d membranes in PDPC mixtures exert a lower counteracting force against the L_o domain bending