Although it is easy to lose one's way when interpreting the many biophysical approaches of analyzing the existence of lipid rafts, few conclusions could be drawn without significant dissent. Model membrane studies are vital in understanding lipid-lipid and lipid-protein interaction, but there is still a long way to go in understanding multicomponent complex biological membranes. This could be analogous to the "three-body problem" where the gravitational interaction of three masses is surprisingly difficult to solve. In the light of information that small transition energies could bring about remarkable structural changes, there may be serious problems in extending model membrane studies to biological membranes. This includes all model membrane studies which support the concept of "detergent-insoluble" complexes to describe lipid rafts. Although diffusion-based studies provide valuable live cell data, they have several drawbacks. It is not easy to interpret results from diffusion data due to a poor understanding of: (1) the diffusion of molecules in complex biological membranes; (2) the ultrastructure of biological membranes; and (3) interaction of the cytoskeleton with biological membranes. Diffusion data might provide a valuable time-kinetics, though it is difficult to deduce structural information from diffusion data with current theoretical understanding. Although homo-FRET-based studies provide an excellent source of structural information on proximity relationships derived by lipidic interactions, the relatively longer time scales of measurement mask the temporal information. In the absence of any ideal "sub-resolution ultra-fast imaging" technique, it is desirable to study chosen model raft components in a model cellular system with available biophysical techniques, and appropriate functional consequences.



anchored protein


cholera toxin B


detergent-insoluble glycolipid




dilauroyl phosphatidylcholine


dipalmitoyl phosphatidylcholine


detergent-resistant membrane


electron microscopy


endoplasmic reticulum


fluorescence correlation spectroscopy






fluorescein phosphatidylethanolamine


fluorescence recovery after photobleaching


Foerster's resonance energy transfer




giant unilamellar vesicle




human coronary artery smooth muscle


lactase-phlorizin hydrolase


methyl- b-cyclodextrin


Madin-Darby canine kidney


neural cell adhesion molecule


nuclear magnetic resonance




polyacrylamide gel electrophoresis




placental alkaline phosphatase


rat basophilic leukemia




single-particle tracking


surface scanning resistance


transient confinement zone


transferrin receptor


trans-Golgi network


yellow fluorescent protein


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