INTERACTIONS OF CHOLESTEROL AND SYNTHETIC STEROLS WITH PHOSPHATIDYLCHOLINES AS DEDUCED FROM INFRARED CH2 WAGGING PROGRESSION INTENSITIES

The intensities of the coupled CH2 wagging vibrations in the IR spectra of relatively ordered phases of phospholipids have been used to characterize acyl chain conformations in a set of sterol/phosphatidylcholine (PC) mixtures. A series of sterols, with side chain lengths at C-17 varying from 0 to 10 carbon atoms, has been synthesized. The thermotropic behavior of 1,2-dipalmitoylphosphatidylcholine (DPPC) with these sterols has been monitored with Fourier transform IR (FT-IR) spectroscopy. As the sterol side chain lengthens, the all-trans conformation of the acyl chains in DPPC persists to progressively higher temperatures. In complementary experiments, cholesterol was mixed with a series of disaturated PCs varying in chain length from C-12 to C22. Remarkable variations in the thermotropic response of the CH2 wagging progression intensity of the PCs were noted at molar ratios of 2:1 (PC/cholesterol). For short-chain PCs (C-12 and C-14) the wagging progressions persisted to 35-40-degrees-C above the main phase transition temperature (T(m)) for the pure phospholipid. In contrast, mixtures of longer chain PCs with cholesterol displayed progressions which vanished close to their respective T(m) values. These trends were unchanged by the presence of a single C=C bond in the acyl chains. A semiquantitative model is used to convert the measured intensity changes into the extent of gauche bond formation in the acyl chains. These results are discussed in terms of structural models for cholesterol/PC interaction. The current investigation represents the first systematic evaluation of conformational changes in model membranes in which both the sterol side chain length and the phospholipid acyl chain length have been varied.