Sphingomyelin and cholesterol: from membrane biophysics and rafts to potential medical applications

Sub-cellular Biochemistry
Yechezkel Barenholz

Abstract

The preferential sphingomyelin-cholesterol interaction which results from the structure and the molecular properties of these two lipids seems to be the physicochemical basis for the formation and maintenance of cholesterol/sphingolipid-enriched nano- and micro-domains (referred to as membrane "rafts") in the plane of plasma and other organelle (i.e., Golgi) membranes. This claim is supported by much experimental evidence and also by theoretical considerations. However, although there is a large volume of information about these rafts regarding their lipid and protein composition, their size, and their dynamics, there is still much to be clarified on these issues, as well as on how rafts are formed and maintained. It is well accepted now that the lipid phase of the rafts is the liquid ordered (LO) phase. However, other (non-raft) parts of the membrane may also be in the LO phase. There are indications that the raft LO phase domains are more tightly packed than the non-raft LO phase, possibly due to intermolecular hydrogen bonding involving sphingolipid and cholesterol. This also explains why the former are detergent-resistant membranes (DRM), while the non-raft LO phase domains are detergent-soluble (sensitive) membranes (DSM)....Continue Reading

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