Research Spotlight: C24:0 and C24:1 Sphingolipids in Cholesterol-Containing, Five- and Six-Component Lipid Membranes

Posted on May 12, 2021

Goni Publication

"C24:0 and C24:1 Sphingolipids in Cholesterol-Containing, Five- and Six-Component Lipid Membranes"

Sphingolipids are important biological lipids and play many roles in cellular processes including being key components in structural membranes. Ceramides are a subfamily of sphingolipids and have received much attention from researchers due to their interesting & unique biophysical properties and important roles as second messengers in signal transduction processes. Much of the biophysical research surrounding the effect of ceramides on membranes has been focused on the C16:0 subspecies because of their relatively large abundance in cells. Evolution in the field of lipidomics has recently revealed that ceramides with other N-alkyl chain lengths, namely C24:0 and C24:1, play important and specific roles in many cell lines. Despite this, few studies have been interested in the biophysical effects of these very-long-chain (VLC, N-acyl chains of 20-24 carbon atoms) ceramides in multicomponent membranes containing cholesterol.

A study of multicomponent membranes is particularly useful when involving ceramides and cholesterol due to their tendency to occupy the same spaces between the lipid acyl chains. While they may want to occupy the same space, the effects that these two lipids have on the membrane are very different. Previously, Dr. Goni’s group reported an interesting effect of C24:1 sphingolipids in multicomponent bilayers containing cholesterol and C16:0 sphingolipids. The stiffening effect of C24:1 sphingolipids was much lower than the C16:0 counterparts and in some cases, they were capable of coexisting in a single gel phase. They postulated that this could be due either to a longer N-acyl chain or the presence of a C=C bond in the unsaturated C24:1 sphingolipid. In this most recent work, the researchers used a series of biophysical techniques to get to the bottom of it.

Differential scanning calorimetry (DSC), confocal fluorescence microscopy, and atomic force microscopy (AFM) were employed to study the biophysics of C24:0 and C24:1 ceramides while interacting with a multi-component membrane consisting of DOPC:sphingomyelin:cholesterol plus 30 mol% of ceramide. The study arrived at several interesting conclusions. C24:0 SM and ceramide act similarly to their shorter chain counterparts with regard to phase separation, membrane stiffening, and increasing transition temperatures. However, these lipids also present some interesting characteristics which may have implications in biological conditions. As examples, combining the 24:0 and 24:1 sphingolipids generated bilayer instability, unusual discrepancies between GUV-AFRM experiments, and exotherms that appeared in some thermotropic transitions. Furthermore, the results revealed that C24:1 SM is a key factor in the distribution of C24 and C24:1 ceramide when both are present in the membrane, and membranes accommodate C24 ceramide more effectively than C16 ceramide in the presence of C24:1 sphingolipids. This study takes several steps towards a better understanding of membrane platform formation in the context of sphingolipid-based signaling cascades.

We would like to thank Dr. Goni for his many contributions to lipid research and for loyally using Avanti lipid products!

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Image Credit: Original Research Publication