Oxidized Phosphatidylcholines Promote Phase Separation of Cholesterol-Sphingomyelin Domains

摘要: Lipid lateral segregation in the plasma membrane is believed to play an important role cell physiology. Sphingomyelin (SM) and cholesterol (Chol)-enriched microdomains have been proposed as liquid-ordered phase platforms that serve to localize signaling complexes modulate intrinsic activities of associated proteins. We modeled domain organization using Langmuir monolayers ternary POPC/SM/Chol well DMPC/SM/Chol mixtures, which exhibit a surface-pressure-dependent miscibility transition coexisting -disordered phases. Using Brewster angle microscopy monolayer compression isotherms, we show presence oxidatively modified phosphatidylcholine, 1-palmitoyl-2-azelaoyl-sn-glydecero-3-phosphocholine, efficiently opposes stabilizes micron-sized separation at lipid packing densities corresponding equilibrium pressure ∼32 mN/m suggested prevail bilayer membranes. This effect ascribed augmented hydrophobic mismatch induced by truncated phosphatidylcholine. To our knowledge, results represent first quantitative estimate relevant level phospholipid oxidation can potentially induce changes its associated functions.