Limits...
Assessing the nature of lipid raft membranes.

Niemelä PS, Ollila S, Hyvönen MT, Karttunen M, Vattulainen I - PLoS Comput. Biol. (2007)

Bottom Line: However, despite the proposed importance of these domains, their properties, and even the precise nature of the lipid phases, have remained open issues mainly because the associated short time and length scales have posed a major challenge to experiments.We also find that the simulated raft bilayers are characterized by nanoscale lateral heterogeneity, though the slow lateral diffusion renders the interpretation of the observed lateral heterogeneity more difficult.The results propose that the functioning of certain classes of membrane proteins is regulated by changes in the lateral pressure profile, which can be altered by a change in lipid content.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Physics, Helsinki University of Technology, Helsinki, Finland. psn@fyslab.hut.fi

ABSTRACT
The paradigm of biological membranes has recently gone through a major update. Instead of being fluid and homogeneous, recent studies suggest that membranes are characterized by transient domains with varying fluidity. In particular, a number of experimental studies have revealed the existence of highly ordered lateral domains rich in sphingomyelin and cholesterol (CHOL). These domains, called functional lipid rafts, have been suggested to take part in a variety of dynamic cellular processes such as membrane trafficking, signal transduction, and regulation of the activity of membrane proteins. However, despite the proposed importance of these domains, their properties, and even the precise nature of the lipid phases, have remained open issues mainly because the associated short time and length scales have posed a major challenge to experiments. In this work, we employ extensive atom-scale simulations to elucidate the properties of ternary raft mixtures with CHOL, palmitoylsphingomyelin (PSM), and palmitoyloleoylphosphatidylcholine. We simulate two bilayers of 1,024 lipids for 100 ns in the liquid-ordered phase and one system of the same size in the liquid-disordered phase. The studies provide evidence that the presence of PSM and CHOL in raft-like membranes leads to strongly packed and rigid bilayers. We also find that the simulated raft bilayers are characterized by nanoscale lateral heterogeneity, though the slow lateral diffusion renders the interpretation of the observed lateral heterogeneity more difficult. The findings reveal aspects of the role of favored (specific) lipid-lipid interactions within rafts and clarify the prominent role of CHOL in altering the properties of the membrane locally in its neighborhood. Also, we show that the presence of PSM and CHOL in rafts leads to intriguing lateral pressure profiles that are distinctly different from corresponding profiles in nonraft-like membranes. The results propose that the functioning of certain classes of membrane proteins is regulated by changes in the lateral pressure profile, which can be altered by a change in lipid content.

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Related in: MedlinePlus

2-D Radial Distribution Functions between the Molecular Center of Mass Positions in SA and SBThe figures show the time evolution in the system at three different time intervals: 0–10 ns (gray, dashed), 30–40 ns (gray), and 90–100 ns (black). The error bars for the black curve indicate the average difference of the two monolayers.
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pcbi-0030034-g003: 2-D Radial Distribution Functions between the Molecular Center of Mass Positions in SA and SBThe figures show the time evolution in the system at three different time intervals: 0–10 ns (gray, dashed), 30–40 ns (gray), and 90–100 ns (black). The error bars for the black curve indicate the average difference of the two monolayers.

Mentions: To judge our findings for lateral heterogeneity, it is worthwhile to stress the slow dynamics in the bilayer plane: despite the extensive time scale simulated, the lateral diffusion coefficients indicate that the molecules move in the plane of the membrane approximately over only their own size within the simulated time scale. Hence, it is evident that the simulation time is not long enough to adequately relax the large-scale structure of the initial configuration and lead to complete mixing of the lipids. The nanoscale heterogeneity observed in this work could thus be debated. However, there is reason to emphasize that while systems SA and SB were started from different initial configurations, they lead to similar conclusions. Further, the small-scale movements of the molecules relative to each other can be characterized; see the 2-D radial distribution functions in Figure 3. The unfavorable close contacts of CHOL–CHOL pairs are revealed by the lowering of the nearest neighbor peak in time. Simultaneously, the secondary peak at 1.0 nm increases, indicating small-scale reorganization of CHOL molecules. Significant changes in time can also be seen in the other plots of Figure 3, revealing the tendency of closer contacts between CHOL–POPC center of mass pairs with respect to PSM–CHOL pairs. In all, this provides further support for lateral reorganization and heterogeneity. The details of the lipid–lipid interactions are related to the widely speculated specific interaction between SM and CHOL, which is discussed elsewhere [57,58].


Assessing the nature of lipid raft membranes.

Niemelä PS, Ollila S, Hyvönen MT, Karttunen M, Vattulainen I - PLoS Comput. Biol. (2007)

2-D Radial Distribution Functions between the Molecular Center of Mass Positions in SA and SBThe figures show the time evolution in the system at three different time intervals: 0–10 ns (gray, dashed), 30–40 ns (gray), and 90–100 ns (black). The error bars for the black curve indicate the average difference of the two monolayers.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1808021&req=5

pcbi-0030034-g003: 2-D Radial Distribution Functions between the Molecular Center of Mass Positions in SA and SBThe figures show the time evolution in the system at three different time intervals: 0–10 ns (gray, dashed), 30–40 ns (gray), and 90–100 ns (black). The error bars for the black curve indicate the average difference of the two monolayers.
Mentions: To judge our findings for lateral heterogeneity, it is worthwhile to stress the slow dynamics in the bilayer plane: despite the extensive time scale simulated, the lateral diffusion coefficients indicate that the molecules move in the plane of the membrane approximately over only their own size within the simulated time scale. Hence, it is evident that the simulation time is not long enough to adequately relax the large-scale structure of the initial configuration and lead to complete mixing of the lipids. The nanoscale heterogeneity observed in this work could thus be debated. However, there is reason to emphasize that while systems SA and SB were started from different initial configurations, they lead to similar conclusions. Further, the small-scale movements of the molecules relative to each other can be characterized; see the 2-D radial distribution functions in Figure 3. The unfavorable close contacts of CHOL–CHOL pairs are revealed by the lowering of the nearest neighbor peak in time. Simultaneously, the secondary peak at 1.0 nm increases, indicating small-scale reorganization of CHOL molecules. Significant changes in time can also be seen in the other plots of Figure 3, revealing the tendency of closer contacts between CHOL–POPC center of mass pairs with respect to PSM–CHOL pairs. In all, this provides further support for lateral reorganization and heterogeneity. The details of the lipid–lipid interactions are related to the widely speculated specific interaction between SM and CHOL, which is discussed elsewhere [57,58].

Bottom Line: However, despite the proposed importance of these domains, their properties, and even the precise nature of the lipid phases, have remained open issues mainly because the associated short time and length scales have posed a major challenge to experiments.We also find that the simulated raft bilayers are characterized by nanoscale lateral heterogeneity, though the slow lateral diffusion renders the interpretation of the observed lateral heterogeneity more difficult.The results propose that the functioning of certain classes of membrane proteins is regulated by changes in the lateral pressure profile, which can be altered by a change in lipid content.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Physics, Helsinki University of Technology, Helsinki, Finland. psn@fyslab.hut.fi

ABSTRACT
The paradigm of biological membranes has recently gone through a major update. Instead of being fluid and homogeneous, recent studies suggest that membranes are characterized by transient domains with varying fluidity. In particular, a number of experimental studies have revealed the existence of highly ordered lateral domains rich in sphingomyelin and cholesterol (CHOL). These domains, called functional lipid rafts, have been suggested to take part in a variety of dynamic cellular processes such as membrane trafficking, signal transduction, and regulation of the activity of membrane proteins. However, despite the proposed importance of these domains, their properties, and even the precise nature of the lipid phases, have remained open issues mainly because the associated short time and length scales have posed a major challenge to experiments. In this work, we employ extensive atom-scale simulations to elucidate the properties of ternary raft mixtures with CHOL, palmitoylsphingomyelin (PSM), and palmitoyloleoylphosphatidylcholine. We simulate two bilayers of 1,024 lipids for 100 ns in the liquid-ordered phase and one system of the same size in the liquid-disordered phase. The studies provide evidence that the presence of PSM and CHOL in raft-like membranes leads to strongly packed and rigid bilayers. We also find that the simulated raft bilayers are characterized by nanoscale lateral heterogeneity, though the slow lateral diffusion renders the interpretation of the observed lateral heterogeneity more difficult. The findings reveal aspects of the role of favored (specific) lipid-lipid interactions within rafts and clarify the prominent role of CHOL in altering the properties of the membrane locally in its neighborhood. Also, we show that the presence of PSM and CHOL in rafts leads to intriguing lateral pressure profiles that are distinctly different from corresponding profiles in nonraft-like membranes. The results propose that the functioning of certain classes of membrane proteins is regulated by changes in the lateral pressure profile, which can be altered by a change in lipid content.

Show MeSH
Related in: MedlinePlus