Abstract
The lipid bilayer of model membranes, liposomes reconstituted from cell lipids, and plasma membrane vesicles and spheres can separate into two distinct liquid phases to yield lipid domains with liquid-ordered and liquid-disordered properties. These observations are the basis of the lipid raft hypothesis that postulates the existence of cholesterol-enriched ordered-phase lipid domains in cell membranes that could regulate protein mobility, localization and interaction. Here we review the evidence that nano-scaled lipid complexes and meso-scaled lipid domains exist in cell membranes and how new fluorescence microscopy techniques that overcome the diffraction limit provide new insights into lipid organization in cell membranes.
Highlights
In the fluid mosaic model (Singer and Nicolson, 1972), the lipid bilayer was originally viewed as a simple 2D fluid in which embedded membrane proteins are able to diffuse freely in the lateral dimension
If the lipid distribution of the plasma membrane is regulated and non-random, this suggests that biophysical processes exist in cells that cause a lateral organization within the membrane and/or active mechanisms have evolved by which cells sort protein and lipids
While the coexistence of micron-scale, resolvable ordered and disordered phase lipid domains was readily observed in model membranes using fluorescence microscopy and phasepartitioning membrane probes (Simons and Vaz, 2004), no such structures have been observed in cell membranes
Summary
In the fluid mosaic model (Singer and Nicolson, 1972), the lipid bilayer was originally viewed as a simple 2D fluid in which embedded membrane proteins are able to diffuse freely in the lateral dimension. While the coexistence of micron-scale, resolvable ordered and disordered phase lipid domains was readily observed in model membranes using fluorescence microscopy and phasepartitioning membrane probes (Simons and Vaz, 2004), no such structures have been observed in cell membranes. Biochemical techniques such as detergent extraction continued to be used (London and Brown, 2000; Shogomori and Brown, 2003), the lack of direct imaging caused the lipid raft hypothesis to become controversial (Munro, 2003; Glebov and Nichols, 2004; Hancock, 2006) and the definition of a lipid raft has evolved over the years. The lack of direct visualization resulted in an emphasis on the sub-diffraction-limited size of the domains such that they were described as being a www.frontiersin.org
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