STUDY BY INFRARED-SPECTROSCOPY OF THE INTERDIGITATION OF C26 0 CEREBROSIDE SULFATE INTO PHOSPHATIDYLCHOLINE BILAYERS/

The insertion mode of the long fatty acid chain of the asymmetric glyc osphingolipid C26:0-cerebroside sulfate (C26-CBS) in symmetric matrice s of phosphatidylcholines of different acyl chain length has been inve stigated by transmission and attenuated total reflectance (ATR) infrar ed spectroscopy. The concentration of 626-CBS in myelin is increased i n the demyelinating disease adrenoleukodystrophy. The conformational o rder and the orientation of the chains of the asymmetric glycosphingol ipid have been evaluated for C25-CBS incorporated at 8 mol % in perdeu terated dimyristoylphosphatidylcholine (DMPC-d(54)) and perdeuterated dipalmitoylphosphatidylcholine (DPPC-d(62)). The results, for the gel phase, are consistent with interdigitation of the C26-CBS long acyl ch ain across the bilayer center of an all-trans-DMPC bilayer in which DM PC is less tilted than in the absence of CBS. In contrast, in DPPC the results suggest that although the CBS long chain interdigitates acros s the center of the bilayer, it does not change the tilt angle of the DPPC molecules in the gel phase. Furthermore, in DPPC, C26-CBS is less well oriented than the host DPPC molecules and it increases the gauch e content of the DPPC acyl chains. The observation of the amide spectr al region indicates that exposure of the sphingosine amide moiety to b uffer is greater in the longer chain length DPPC bilayer than in the s horter chain length DMPC bilayer. The thermotropic behavior of the lip id mixtures of C26-CBS at 8 mol % in DMPC or DPPC shows that the glyco sphingolipid stabilizes the gel phase of the short chain length bilaye r while it destabilizes the long chain length one. Our results further demonstrate that, at this concentration, C26-CBS is completely miscib le in DMPC and DPPC in the gel and the liquid crystalline phases. The difference in behavior of C26-CBS in DMPC and DPPC is a consequence of the greater mismatch between the C26 chain length and the bilayer thi ckness of DPPC relative to DMPC. They may help to understand the delet erious effects of glycosphingolipids with very long chain fatty acids in adrenoleukodystrophy.