Which component of the membrane forms lipid rafts?
Lipid raft genesis requires cooperative interaction two distinct lipid classes rather than single component protein scaffold alone driven thermodynamics enthalpy. Sphingolipids sphingomyelin glycosylceramide ganglioside with amide linked saturated acyl chains eighteen to twenty four carbons sphingosine backbone capable hydrogen bond donor acceptor network adopt extended conformation high melting temperature promoting condensation ordered domain formation. Cholesterol planar rigid ring three beta hydroxyl inserts voids between chains increasing order parameter thickness three point seven to four point four nanometers creating liquid ordered phase coexisting liquid disordered phosphatidylcholine phosphatidylethanolamine pools rich unsaturated tails kinked. Thermodynamic driving force favorable enthalpy van der Waals CH pi interactions outweighing entropy mixing observed ternary model membranes DOPC SM cholesterol forming domains ten to two hundred nanometers AFM fluorescence super resolution STED microscopy visualizing. Phosphatidylcholine unsaturated kink cardiolipin four chains mitochondrial inner membrane excluded rafts distinct organelle. Cholesterol sphingolipids combination therefore defines physical basis raft formation underlying sorting apical proteins GPI anchored signaling kinases pathogen entry HIV influenza Ebola mechanisms studied modern cell biology raft concepts fundamental exams and membrane microdomain investigations contemporary biophysics and virology and immunology research focus.
Ref: Sezgin et al., Biochim Biophys Acta 2017, Cholesterol sphingolipid cooperation forms lipid rafts domains and phase separation.