Using cyclodextrin-induced lipid substitution to study membrane lipid and ordered membrane domain (raft) function in cells

Methods for efficient cyclodextrin-induced lipid exchange have been developed in our lab. These make it possible to almost completely replace the lipids in the outer leaflet of artificial membranes or the plasma membranes of living cells with exogenous lipids. Lipid replacement/substitution allows detailed studies of how lipid composition and asymmetry influence the structure and function of membrane domains and membrane proteins. In this review, we both summarize progress on cyclodextrin exchange in cells, mainly by the use of methyl-alpha cyclodextrin to exchange phospholipids and sphingolipids, and discuss the issues to consider when carrying out lipid exchange experiments upon cells. Issues that impact interpretation of lipid exchange are also discussed. This includes how overly naïve interpretation of how lipid exchange-induced changes in domain formation can impact protein function.