Membrane Organization and Lipid Rafts
Abstract
Cell membranes are composed of a lipid bilayer, containing proteins that span the bilayer and/or interact with the lipids on either side of the two leaflets. Although recent advances in lipid analytics show that membranes in eukaryotic cells contain hundreds of different lipid species, the function of this lipid diversity remains enigmatic. The basic structure of cell membranes is the lipid bilayer, composed of two apposing leaflets, forming a two-dimensional liquid with fascinating properties designed to perform the functions cells require. To coordinate these functions, the bilayer has evolved the propensity to segregate its constituents laterally. This capability is based on dynamic liquid–liquid immiscibility and underlies the raft concept of membrane subcompartmentalization. This principle combines the potential for sphingolipid-cholesterol self-assembly with protein specificity to focus and regulate membrane bioactivity. Here we will review the emerging principles of membrane architecture with special emphasis on lipid organization and domain formation.
All cells are delimited by membranes, which confer them spatial identity and define the boundary between intracellular and extracellular space. These membranes are composed of lipids and proteins. The propensity of the hydrophobic moieties of lipids to self-associate and the tendency of the hydrophilic moieties to interact with aqueous environments and with each other is the physical basis of the spontaneous formation of the lipid bilayer of cell membranes. This principle of amphipathicity of lipids is the chemical property that enables the cells to segregate their internal constituents from the external environment. This same principle acts at the subcellular level to assemble the membranes surrounding each cellular organelle. About one-third of the genome encodes membrane proteins, and many other proteins spend part of their lifetime bound to membranes. Membranes are the sites where many cellular machineries carry out their function.
This remarkable liquid with its amphipathic constituents is attracting increasing attention not only by biologists but also by physicists because of its fascinating properties. Membrane research has picked up speed in recent years. An increasing number of atomic structures of membrane proteins are being solved, the field of lipid research is exploding, and the principles of membrane organization are being overhauled. New insights into the staggering capability of cell membranes to subcompartmentalize have revealed how membranes support intracellular membrane trafficking and parallel processing of signaling events.
Here we will review the emerging principles of membrane architecture with special emphasis on lipid organization and domain formation.
Sphingolipids (SPs) and sterols enable eukaryotic cellular membranes with the property of vesicular trafficking important for the establishment and maintenance of distinct organelles. Tissue-specific SPs in higher organisms enable the generation of specific architecture and function
ACKNOWLEDGMENTS
We thank Hermann-Josef Kaiser and Ilya Levental for reading the paper and the Simons lab for continuous critical input. We also thank Doris Meder, especially for drawing Figure 3. This work was supported by DFG “Schwerpunktprogramm1175” Grant no. SI459/2-1, DFG “Transregio 83” Grant no. TRR83 TP02, BMBF “ForMaT” Grant no. 03FO1212, ESF “LIPIDPROD” Grant no. SI459/3-1, and the Klaus Tschira Foundation.