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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Lateral Pressure Profiles of Systems SA and SB (Top) and of Previously Simulated Pure POPC/PSM Systems and a Binary DPPC–CHOL System (Bottom)The center of the membrane is at z = 0. The graphs have been averaged to be symmetric on both sides of the center and smoothed by adaptive high-order spline fitting [90]. Error bars are statistical errors for each slab. The errors have been shown for only one of the monolayers of the DPPC–CHOL system because they are equal for both monolayers and also smaller or equal for the other systems.
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pcbi-0030034-g004: Lateral Pressure Profiles of Systems SA and SB (Top) and of Previously Simulated Pure POPC/PSM Systems and a Binary DPPC–CHOL System (Bottom)The center of the membrane is at z = 0. The graphs have been averaged to be symmetric on both sides of the center and smoothed by adaptive high-order spline fitting [90]. Error bars are statistical errors for each slab. The errors have been shown for only one of the monolayers of the DPPC–CHOL system because they are equal for both monolayers and also smaller or equal for the other systems.

Mentions: Structure and dynamics of membrane proteins are likely to be influenced by the lateral pressure profile, which has been proposed as a mechanism for, e.g., general anesthesia [20,59]. To elucidate this issue, we computed the lateral pressure profiles of various lipid membrane systems (see Figure 4). For a discussion of the coupling of the peaks in the lateral pressure profile with the molecular groups and different interaction types, see previous related simulation studies [19,60–63]. Here, we focus on a more generic issue, that is, the joint effect of CHOL and PSM on the pressure profile.


Assessing the nature of lipid raft membranes.

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

Lateral Pressure Profiles of Systems SA and SB (Top) and of Previously Simulated Pure POPC/PSM Systems and a Binary DPPC–CHOL System (Bottom)The center of the membrane is at z = 0. The graphs have been averaged to be symmetric on both sides of the center and smoothed by adaptive high-order spline fitting [90]. Error bars are statistical errors for each slab. The errors have been shown for only one of the monolayers of the DPPC–CHOL system because they are equal for both monolayers and also smaller or equal for the other systems.
© Copyright Policy
Related In: Results  -  Collection

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

pcbi-0030034-g004: Lateral Pressure Profiles of Systems SA and SB (Top) and of Previously Simulated Pure POPC/PSM Systems and a Binary DPPC–CHOL System (Bottom)The center of the membrane is at z = 0. The graphs have been averaged to be symmetric on both sides of the center and smoothed by adaptive high-order spline fitting [90]. Error bars are statistical errors for each slab. The errors have been shown for only one of the monolayers of the DPPC–CHOL system because they are equal for both monolayers and also smaller or equal for the other systems.
Mentions: Structure and dynamics of membrane proteins are likely to be influenced by the lateral pressure profile, which has been proposed as a mechanism for, e.g., general anesthesia [20,59]. To elucidate this issue, we computed the lateral pressure profiles of various lipid membrane systems (see Figure 4). For a discussion of the coupling of the peaks in the lateral pressure profile with the molecular groups and different interaction types, see previous related simulation studies [19,60–63]. Here, we focus on a more generic issue, that is, the joint effect of CHOL and PSM on the pressure profile.

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