Ceramide: A simple sphingolipid with unique biophysical properties

Ceramides are involved in a variety of cellular processes and in disease. Their biological functions are thought to depend on ceramides’ unique biophysical properties, which promote strong alterations of cell membrane properties and consequent triggering of signaling events. Over the last decades, efforts were made to understand the impact of ceramide on membrane biophysical features. Several studies, performed in a multitude of membrane models, address ceramides’ specific interactions, the effect of their acyl chain structure and the influence of membrane lipid composition and properties on ceramide biophysical outcome. In this review, a rationale for the multiple and complex changes promoted by ceramide is provided, highlighting, on a comprehensive and critical manner, the interactions between ceramides and specific lipids and/or lipid phases. Focus is also given to the interplay between ceramide and cholesterol, particularly in lipid raft-mimicking mixtures, an issue of intense debate due to the urgent need to understand the biophysical impact of ceramide formation in models resembling the cell membrane. The implications of ceramide-induced biophysical changes on lipid–protein interactions and cell signaling are also discussed, together with the emerging evidence for the existence of ceramide-gel like domains in cellular membranes.