Different Effects of Long- and Short-Chain Ceramides on the Gel-Fluid and Lamellar-Hexagonal Transitions of Phospholipids: A Calorimetric, NMR, and X-Ray Diffraction Study

Abstract

The effects on dielaidoylphosphatidylethanolamine (DEPE) bilayers of ceramides containing different N-acyl chains have been studied by differential scanning calorimetry small angle x-ray diffraction and (31)P-NMR spectroscopy. N-palmitoyl (Cer16), N-hexanoyl (Cer6), and N-acetyl (Cer2) sphingosines have been used. Both the gel-fluid and the lamellar-inverted hexagonal transitions of DEPE have been examined in the presence of the various ceramides in the 0-25 mol % concentration range. Pure hydrated ceramides exhibit cooperative endothermic order-disorder transitions at 93 degrees C (Cer16), 60 degrees C (Cer6), and 54 degrees C (Cer2). In DEPE bilayers, Cer16 does not mix with the phospholipid in the gel phase, giving rise to high-melting ceramide-rich domains. Cer16 favors the lamellar-hexagonal transition of DEPE, decreasing the transition temperature. Cer2, on the other hand, is soluble in the gel phase of DEPE, decreasing the gel-fluid and increasing the lamellar-hexagonal transition temperatures, thus effectively stabilizing the lamellar fluid phase. In addition, Cer2 was peculiar in that no equilibrium could be reached for the Cer2-DEPE mixture above 60 degrees C, the lamellar-hexagonal transition shifting with time to temperatures beyond the instrumental range. The properties of Cer6 are intermediate between those of the other two, this ceramide decreasing both the gel-fluid and lamellar-hexagonal transition temperatures. Temperature-composition diagrams have been constructed for the mixtures of DEPE with each of the three ceramides. The different behavior of the long- and short-chain ceramides can be rationalized in terms of their different molecular geometries, Cer16 favoring negative curvature in the monolayers, thus inverted phases, and the opposite being true of the micelle-forming Cer2. These differences may be at the origin of the different physiological effects that are sometimes observed for the long- and short-chain ceramides.

Changes in membrane biophysical properties induced by sphingomyelinase depend on the sphingolipid N-acyl chain

“…To date, several biophysical studies [e.g., (13)(14)(15)(16)(17)(18)(19)] have focused on the effect of Cer on the properties of model membranes and have demonstrated that Cer increases the global order of the membrane and promotes lateral phase separation in a manner dependent on its acyl chain structure (19)(20)(21). However, no information is currently available on the effect of altering the Cer acyl chain length on the properties of cell membranes.…”

Developmentally Regulated Ceramide Synthase 6 Increases Mitochondrial Ca2+ Loading Capacity and Promotes Apoptosis

“…Another study re-vealed a specific role for dihydro-C 16:0 -ceramide in the adaptive cardiac tissue response to hypoxia (74). Although certain ceramide species could have different effects on biophysical properties of the membrane lipid bilayer (75), it remains unclear how ceramides containing different fatty acids exert their effects upon cell physiology. These studies suggest that regulated expression of specific CerS in intracellular compartments in conjunction with availability of certain fatty acylCoA species could be an important mechanism for controlling the fatty acid composition of ceramides and their biological effects on cell metabolism.…”

Ceramide synthase 5 mediates lipid-induced autophagy and hypertrophy in cardiomyocytes

“…This notion is based on data from the literature that indicate that sphingolipid N-acyl chain lengths alter the biophysical properties of membranes, including curvature, fluidity, stability, and permeability (58)(59)(60)(61)(62)(63)(64)(65). In particular, it has been shown that genetic ablation of CerS2 in mice promoted membrane fusion and budding (66).…”