MODULATION OF PHOSPHOLIPID ACYL CHAIN ORDER BY CHOLESTEROL - A SOLID-STATE H-2 NUCLEAR-MAGNETIC-RESONANCE STUDY

The effect of cholesterol on the acyl chain order of three glycerophosphocholines with 14, 16, and 18 carbons per acyl chain, namely, di(14:0)PC, di(16:0)PC, and di(18:0)PC, above the gel to liquid-crystalline phase transition temperature was investigated by using 2H nuclear magnetic resonance spectroscopy. Average acyl chain lengths were calculated from the segmental order parameters (Smol) for the sn-1 and the sn-2 chains in the absence of cholesterol and at 3:1, 2:1, and 1:1 mole ratios of phospholipid–cholesterol. The three binary mixtures of cholesterol with phosphatidylcholines are in the liquid-ordered (lo) phase. For all the three phosphatidylcholine–cholesterol systems, the distance from the carbonyl groups to the terminal methyl groups is shorter than the length of the cholesterol molecule. A molecular model for the lo phase consistent with these observations has in a statistical sense a part of each cholesterol molecule in one monolayer extending into the other monolayer. This results in a packing arrangement akin to that in interdigitated systems. On the basis of the effect of cholesterol on phospholipid acyl chain orientational order, it is suggested that the liquid-disordered (ld) phase at low cholesterol concentrations corresponds to a packing mode in which the cholesterol molecule spans the entire transbilayer hydrophobic region. A molecular mechanism is proposed in which increasing the concentration of cholesterol has the effect of stretching the acyl chains of phospholipids by increasing the population of trans conformers up to a stage where the hydrophobic length is considerably longer than the cholesterol molecule. Beyond this concentration, the partially interdigitated phase forms. This interpretation provides a molecular basis for the liquid-crystalline phase immiscibility in cholesterol-containing bilayers where the partially interdigitated phase corresponds to the liquid-ordered phase (lo) and the noninterdigitated phase corresponds to the liquid-disordered (ld) phase. It is suggested that the fluid phase immiscibility exhibited by cholesterol-containing lipid bilayers follows as a natural consequence of the length mismatch between the essentially rigid steroid and the flexible phospholipid acyl chains and that there is no need to invoke complex formation between the two components of this binary system. © 1990, American Chemical Society. All rights reserved.