Model lipid raft

The lipid membrane provides shelter for membrane proteins to do their functions. However, instead of working alone, membrane proteins such as ion channels work together with the membrane, such that the lipid composition around the protein actually affects the activation and the functioning of the protein. This idea is largely the essence of the lipid raft model (8), which highlights the importance of lipids in a variety of cellular functions. It has been observed, for example, that rhodopsin, which is the light sensitive membrane protein, favors interactions with polyunsaturated lipids (9). 

There are two views of the motion of integral proteins in the bilayer. In the fluid mosaic model shown in Fig. 11.53, the proteins are mobile, but their diffusion coefficients are much smaller than those of the lipids. In the lipid raft model, a number of lipid and cholesterol molecules form ordered structures, or rafts, that envelop proteins and help carry them to specific parts of the cell. 

Distinguish between the fluid mosaic and lipid raft models for motion of integral proteins in a biological membrane. 

While the fluid mosaic model of membrane stmcture has stood up well to detailed scrutiny, additional features of membrane structure and function are constantly emerging. Two structures of particular current interest, located in surface membranes, are tipid rafts and caveolae. The former are dynamic areas of the exo-plasmic leaflet of the lipid bilayer enriched in cholesterol and sphingolipids they are involved in signal transduction and possibly other processes. Caveolae may derive from lipid rafts. Many if not all of them contain the protein caveolin-1, which may be involved in their formation from rafts. Caveolae are observable by electron microscopy as flask-shaped indentations of the cell membrane. Proteins detected in caveolae include various components of the signal-transduction system (eg, the insutin receptor and some G proteins), the folate receptor, and endothetial nitric oxide synthase (eNOS). Caveolae and lipid rafts are active areas of research, and ideas concerning them and their possible roles in various diseases are rapidly evolving. 

The most likely way for pardaxin molecules to insert across the membrane in an antiparallel manner is for them to form antiparallel aggregates on the membrane surface that then insert across the membrane. We developed a "raft"model (data not shown) that is similar to the channel model except that adjacent dimers are related to each other by a linear translation instead of a 60 rotation about a channel axis. All of the large hydrophobic side chains of the C-helices are on one side of the "raft" and all hydrophilic side chains are on the other side. We postulate that these "rafts" displace the lipid molecules on one side of the bilayer. When two or more "rafts" meet they can insert across the membrane to form a channel in a way that never exposes the hydrophilic side chains to the lipid alkyl chains. The conformational change from the "raft" to the channel structure primarily involves a pivoting motion about the "ridge" of side chains formed by Thr-17, Ala-21, Ala-25, and Ser-29. These small side chains present few steric barriers for the postulated conformational change. 

Edidin, M. The state of lipid rafts from model membranes to cells. Ann. Rev. Biophys. Biomol. Struct. 2003, 32, 257-83. 

McMullen, T.P.W., Lewis, R.N.A.H., McElhaney, R.N. Cholesterol-phospholipid interactions, the liquid-ordered phase and lipid rafts in model and biological membranes. Curr. Opin. Colloid Interface Sci. 2004, 8, 459-68. 

Borner et al. (2005) took a different approach to address the specific localization of DRM proteins to lipid rafts. In this smdy the relative enrichment of proteins in the detergent-resistant fraction versus total cell membranes was used as a measure of the specificity of putative lipid raft proteins. In their study Bomer et al. used Arabidopsis thaliana as the model system so a direct comparison with mammalian DRM reports is difficult and perhaps unfair since it is not always clear what the human homologue of a plant protein is. However, it is interesting to note that Bomer et al. also found that the common contaminants in DRMs are certain highly abundant mitochondrial and endoplasmic reticulum proteins. 

Zeyda, M. and Stulnig, T.M. (2006) Lipid Rafts Co. an integrated model of membrane organization in T cell activation. Prog. Lipid Res. 45, 187-202. 

Dietrich C, BagatolU LA, Volovyk ZN, Thompson NL, Levi M, Jacobson K, Gratton E. Lipid rafts reconstituted in model membranes. Biophys. J. 2001 80 1417-1428. 

Phase separation in model lipid membranes is established clearly (120), but the significance of lipid rafts in cell membranes has been controversial (121) largely because of their isolation by harsh conditions of detergent resistance. More recently, methods have been developed to visualize lipid rafts in living cells (122, 123) and to identify proteins within them by less invasive methods (124). 

Crane JM, Tamm LK. Role of cholesterol in the formation and nature of lipid rafts in planar and spherical model membranes. Biophys. J. 2004 86 2965-2979. 

Lipid rafts on cell membranes are cholesterol- and sphingolipid-rich domains that function as platforms for signal transduction and other cellular processes [6], Tethered lipid bilayers have been proposed as a promising model membrane to describe the structure and function of cell membratKs [7]. Based on these facts, we endeavor to array the lipid rafts as a form of tethered bilayer lipid membrare into the nanopattemed substrates to generate a raft membrane-based biosensing platform (Fig. Ic). 

Keywords cell signaling lipid rafts BAR domains membrane curvature membrane elasticity PIP2 diffusion mean-field model coarse-grained theory Poisson-Boltzmann theory Cahn-Hilliard equations... 

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