Principles of microdomain formation in biological membranes— Are there lipid liquid ordered domains in living cellular membranes?

Abstract

Recently, there has been considerable controversy surrounding lipid rafts contained in the plasma membrane. It has been suggested that these microdomains enriched in cholesterol and sphingolipids could play an important role in many cellular processes including signal transduction, membrane trafficking, cytoskeletal organization, and pathogen entry. However, rafts have proven difficult to visualize in living cells. Most of the evidence for their existence relies on indirect, and sometimes even inadequate, methods such as detergent extraction. Direct studies of the distribution of putative raft components in living cells have not yet reached a consensus on the size, or even the presence, of these microdomains, and hence it seems that a definitive proof of raft existence has yet to be obtained.
As is the case in every highly disputed field, the number of models, counter models, explanations, and theories at the heart of the lipid raft controversy has lead to a great deal of confusion. In this review, we will attempt to provide a summary of the different models of membrane microdomains, including lipid rafts, as well as the methods used in their study, and their short falls. Furthermore, we will try to describe some promising new investigative methods that should be able to shed a great amount of light on some of the most controversial aspects of lipid raft research, mainly, whether they actually do exist.