Effect of Sterol Structure on Ordered Lipid Domains in Symmetric and Asymmetric Model Membranes

Abstract

The packing of ordered sterol-sphingolipid-rich liquid ordered domains in biomembranes is greatly impacted by sterol structure. For this reason, the dependence of biological functions upon sterol structure can be used to identify processes likely to be dependent upon ordered domain formation. In this study we compared the effect of sterol structure upon ordered domain formation in symmetric vesicles composed of a mixture of sphingomyelin, 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and cholesterol, to that in asymmetric vesicles in which sphingomyelin was introduced into only the outer leaflet of vesicles composed of DOPC and cholesterol. In most cases, sterol behavior was similar in symmetric and asymmetric vesicles, with ordered domains being most strongly stabilized by 7-dehydrocholesterol and cholesterol, to a moderate degree by lanosterol, epicholesterol and desmosterol, and very little if at all by 4-cholesten-3-one. However, we found that in asymmetric vesicles desmosterol stabilizes ordered domain almost as well as cholesterol, and stabilizes ordered domains to a much greater degree than epicholesterol. From previous studies using symmetric vesicles and a different lipid composition, we had come to the opposite conclusion: that epicholesterol stabilizes ordered domains similarly to cholesterol and to a greater degree than desmosterol. Based on behavior in asymmetric membranes, which mimic cell membranes more closely than symmetric membranes, we have re-evaluated our prior endocytosis and bacterial uptake studies and now conclude that sterol raft-forming ability may be the sole structural property of sterol that is necessary for these functions.