The insertion mode of the long
fatty acid chain of the asymmetric
glycosphingolipid C26:0-
cerebroside sulfate (C26-CBS) in symmetric matrices of
phosphatidylcholines of different acyl chain length has been investigated by transmission and attenuated total reflectance (ATR) infrared spectroscopy. The concentration of C26-CBS in myelin is increased in the
demyelinating disease adrenoleukodystrophy. The conformational order and the orientation of the chains of the asymmetric
glycosphingolipid have been evaluated for C26-CBS incorporated at 8 mol % in perdeuterated
dimyristoylphosphatidylcholine (DMPC-d54) and perdeuterated
dipalmitoylphosphatidylcholine (DPPC-d62). The results, for the gel phase, are consistent with interdigitation of the C26-CBS long acyl chain across the bilayer center of an all-trans-
DMPC bilayer in which
DMPC is less tilted than in the absence of CBS. In contrast, in DPPC the results suggest that although the CBS long chain interdigitates across 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 gauche content of the DPPC acyl chains. The observation of the
amide spectral region indicates that exposure of the
sphingosine amide moiety to
buffer is greater in the longer chain length DPPC bilayer than in the shorter chain length
DMPC bilayer. The thermotropic behavior of the
lipid mixtures of C26-CBS at 8 mol % in
DMPC or DPPC shows that the
glycosphingolipid stabilizes the gel phase of the short chain length bilayer while it destabilizes the long chain length one. Our results further demonstrate that, at this concentration, C26-CBS is completely miscible 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 thickness of DPPC relative to
DMPC. They may help to understand the deleterious effects of
glycosphingolipids with very long chain
fatty acids in
adrenoleukodystrophy.