Effect of hydrophobic mismatch and interdigitation on sterol/sphingomyelin interaction in ternary bilayer membranes

Abstract

Sphingomyelin (SM) is a major phospholipid in most cell membranes. SMs are composed of a long-chain base (often sphingosine, 18:1(Δ4t)), and N-linked acyl chains (often 16:0, 18:0 or 24:1(Δ15c)). Cholesterol interacts with SM in cell membranes, but the acyl chain preference of this interaction is not fully elucidated. In this study we have examined the effects of hydrophobic mismatch and interdigitation on cholesterol/sphingomyelin interaction in complex bilayer membranes. We measured the capacity of cholestatrienol (CTL) and cholesterol to form sterol-enriched ordered domains with saturated SM species having different chain lengths (14 to 24 carbons) in ternary bilayer membranes. We also determined the equilibrium bilayer partitioning coefficient of CTL with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) membranes containing 20mol% of saturated SM analogs. Ours results show that while CTL and cholesterol formed sterol-enriched domains with both short and long-chain SM species, the sterols preferred interaction with 16:0-SM over any other saturated chain length SM analog. When CTL membrane partitioning was determined with fluid POPC bilayers containing 20mol% of a saturated chain length SM analog, the highest affinity was seen with 16:0-SM (both at 23 and 37°C). These results indicate that hydrophobic mismatch and/or interdigitation attenuate sterol/SM association and thus affect lateral distribution of sterols in the bilayer membrane.

Inhibitory effect of dietary lipids on chaperone-mediated autophagy

“…Thus, in the HFD group, we did not observe an increase in cholesterol levels; instead, the elevated levels of short saturated CER and SM species detected in this group may promote the formation of even tighter domains (38,39). It is well established that CER and phospholipids with polyunsaturated fatty acid chains, which are also elevated in the lysosomal membrane of HFD mice, do not mix well with cholesterol and form domains with different lipid packing than those of cholesterol, which may promote the concentration of specific proteins in these domains (40).…”

Unique thermal behavior of sphingomyelin species with nonhydroxy and 2-hydroxy very-long-chain (C28-C32) PUFAs

“…The experiments with ternary DOPC:cholesterol:SM systems, one evaluating the quenching of DPH fl uorescence by 10-SLPC and the other one following the distribution of the fl uorescent probe DiI in GUVs, proved correct our initial presumption that the n-V and h-V SMs would be "resistant" to segregate into cholesterol/SM-rich domains when they are in coexistence with cholesterol, at least at temperatures at which most other SM species typically do (see for example (23) and references therein).…”

Synthesis of Gb3 Glycosphingolipids with Labeled Head Groups: Distribution in Phase‐Separated Giant Unilamellar Vesicles

“…However,the l o phase consists not only of SM but also of Chol owing to its better solubility in SM membranes than in PC membranes. [55][56][57] Chol is best soluble in SM C 16:0 . [56,57] If the solubility of Chol in the l o phase greatly influenced the Gb 3 distribution in the l o phase,the opposite trend would have been observed.…”

“…[55][56][57] Chol is best soluble in SM C 16:0 . [56,57] If the solubility of Chol in the l o phase greatly influenced the Gb 3 distribution in the l o phase,the opposite trend would have been observed. This trend was not found and agrees with the idea that the interaction of Gb 3 with Chol is less important than the one with SM.…”