| Abstract
| - Naturally occurring long-chain ceramides (Cer) are known to alter the lateral organization of biological membranes.In particular, they produce alterations of microdomains that are involved in several cellular processes, ranging fromapoptosis to immune response. In order to induce similar biological effects, short-chain Cer are extensively used inin vivo experiments to replace their long-chain analogues. In this work, we used the combined approach of atomicforce microscopy (AFM) and fluorescence correlation spectroscopy (FCS) to investigate the effect of Cer chain lengthin lipid bilayers composed of sphingomyelin, dioleoyl-phosphatidylcholine, and cholesterol. Our results show thatonly long-chain Cer, like C18 and C16, are able to segregate from the liquid-ordered phase, forming separate Cer-enriched domains. Conversely, short-chain Cer do not form a separate phase but alter the physical properties of theliquid-ordered domains, decreasing their stability and viscosity and perturbing the lipid packing. These differencesmay contribute to the explanation of the different physiological effects that are often observed for the long- andshort-chain Cer.
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