Abstract
Lipid rafts are microdomains rich in sphingomyelin (SM) and cholesterol (Chol). The essential question is why natural lipid rafts prefer SM rather than saturated diacyl glycerophosphocholine, although both form ordered membranes with Chol in model systems. Hence in this study, we synthesized site-specifically deuterated 1-palmitoyl-2-stearoyl-sn-glycero-3-phosphocholines that match the acyl chain length of stearoyl-SM (SSM), and compared their deuterium quadrupole coupling profiles in detail. The results suggest a deeper distribution of Chol in the SSM membranes, a lower entropic penalty upon accommodation of Chol in SSM membranes, and a higher thermal stability of acyl-chain orders in the SSM-Chol bilayers than in the 1-palmitoyl-2-stearoyl-sn-glycero-3-phosphocholine-Chol system at various Chol concentrations. The entropy effect and thermal stability should render SM a more preferred raft constituent than saturated diacyl glycerophosphocholine. Our data also demonstrate that the selective and comprehensive deuteration strategy is indispensable for accurate comparison of order profiles.