Content area
Full Text
ABSTRACT Atomic force microscopy has been used to study the distribution of ganglioside GM1 in model membranes composed of ternary lipid mixtures that mimic the composition of lipid rafts. The results demonstrate that addition of 1 % GM1 to 1:11:1 sphingomyelin/dioleoylphosphatidylcholine/cholesterol monolayers leads to the formation of small ganglioside-rich microdomains (40-100 nm in size) that are localized preferentially in the more ordered sphingomyelin/cholesterol-rich phase. With 5% GM1 some GM1 microdomains are also detected in the dioleoylphosphatidylcholine-rich phase. A similar preferential localization of GMI in the ordered phase is observed for bilayers with the same ternary lipid mixture in the upper leaflet. The small GM1 -rich domains observed in these experiments are similar to the sizes for lipid rafts in natural membranes but considerably smaller than the ordered bilayer domains that have been shown to be enriched in GM1 in recent fluorescence microscopy studies of lipid bilayers. The combined data from a number of studies of model membranes indicate that lateral organization occurs on a variety of length scales and mimics many of the properties of natural membranes.
INTRODUCTION
Implications for natural membranes
The size of the GM1-microdomains observed in our studies is comparable with estimates for the size of lipid rafts in natural membranes (Jacobson and Dietrich, 1999). Many of these studies have examined the localization of glycolipids or GPI-linked proteins, suggesting that the estimated size of the "rafts" reflects the organization of these species within a larger liquid-ordered SPM/cholesterol-rich phase. In this context it is interesting to note that the putative functional role of lipid rafts seems to require them to be small dynamic platforms, similar to what is observed here. The role of glycolipid aggregation in determining raft size and function also nicely accommodates the problem of understanding the size, location, and stability of such small domains in plasma membranes that contain relatively large amounts of both SPM and cholesterol. Previous work had suggested that the cytoskeleton might play a significant role in regulating raft size in natural membranes (Dietrich et al., 2001; Jacobson and Dietrich, 1999). Whereas the present results do not preclude this, they do indicate that glycolipid aggregation may in fact be sufficient to account for many of the observed phenomena. For example, glycolipids have been shown to be...