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Role of lipids in spheroidal high density lipoproteins.

Vuorela T, Catte A, Niemelä PS, Hall A, Hyvönen MT, Marrink SJ, Karttunen M, Vattulainen I - PLoS Comput. Biol. (2010)

Bottom Line: Yet, not only the conformations but also the dynamics of lipids are found to be distinctly different in the different regions of HDL, highlighting the importance of dynamics in considering the functionalization of HDL.Our results reveal that not only hydrophobicity but also conformational entropy of the molecules are the driving forces in the formation of HDL structure.The results provide the first detailed structural model for HDL and its dynamics with and without apoA-I, and indicate how the interplay and competition between entropy and detailed interactions may be used in nanoparticle and drug design through self-assembly.

View Article: PubMed Central - PubMed

Affiliation: Department of Physics, Tampere University of Technology, Tampere, Finland.

ABSTRACT
We study the structure and dynamics of spherical high density lipoprotein (HDL) particles through coarse-grained multi-microsecond molecular dynamics simulations. We simulate both a lipid droplet without the apolipoprotein A-I (apoA-I) and the full HDL particle including two apoA-I molecules surrounding the lipid compartment. The present models are the first ones among computational studies where the size and lipid composition of HDL are realistic, corresponding to human serum HDL. We focus on the role of lipids in HDL structure and dynamics. Particular attention is paid to the assembly of lipids and the influence of lipid-protein interactions on HDL properties. We find that the properties of lipids depend significantly on their location in the particle (core, intermediate region, surface). Unlike the hydrophobic core, the intermediate and surface regions are characterized by prominent conformational lipid order. Yet, not only the conformations but also the dynamics of lipids are found to be distinctly different in the different regions of HDL, highlighting the importance of dynamics in considering the functionalization of HDL. The structure of the lipid droplet close to the HDL-water interface is altered by the presence of apoA-Is, with most prominent changes being observed for cholesterol and polar lipids. For cholesterol, slow trafficking between the surface layer and the regimes underneath is observed. The lipid-protein interactions are strongest for cholesterol, in particular its interaction with hydrophobic residues of apoA-I. Our results reveal that not only hydrophobicity but also conformational entropy of the molecules are the driving forces in the formation of HDL structure. The results provide the first detailed structural model for HDL and its dynamics with and without apoA-I, and indicate how the interplay and competition between entropy and detailed interactions may be used in nanoparticle and drug design through self-assembly.

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Diffusion coefficients of the lipid components.Each point in the plot describes the diffusion coefficient for one of the lipid types. The distance  is the average distance of the given lipid from the COM of the particle. To facilitate comparison between core (three-dimensional diffusion) and surface lipids (two-dimensional diffusion), the coefficients have been scaled with , where  is the dimension of the fit (either two or three).
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pcbi-1000964-g006: Diffusion coefficients of the lipid components.Each point in the plot describes the diffusion coefficient for one of the lipid types. The distance is the average distance of the given lipid from the COM of the particle. To facilitate comparison between core (three-dimensional diffusion) and surface lipids (two-dimensional diffusion), the coefficients have been scaled with , where is the dimension of the fit (either two or three).

Mentions: Figure 6 depicts how the diffusion rate varies significantly inside the lipid droplet and/or full HDL. The diffusion is the slowest in the middle of the particle, it speeds up as the molecules get closer to the interface, and the fastest diffusion is found at the interface. The influence of apoA-I on diffusion of lipids is modest. It turns out that the lipid diffusion coefficients in the protein-free lipid droplet and the full HDL particle are almost similar. The apoA-I proteins may slow down the diffusion of lipids slightly especially close to the interfacial regions. The effect is, however, weak (see Table 2).


Role of lipids in spheroidal high density lipoproteins.

Vuorela T, Catte A, Niemelä PS, Hall A, Hyvönen MT, Marrink SJ, Karttunen M, Vattulainen I - PLoS Comput. Biol. (2010)

Diffusion coefficients of the lipid components.Each point in the plot describes the diffusion coefficient for one of the lipid types. The distance  is the average distance of the given lipid from the COM of the particle. To facilitate comparison between core (three-dimensional diffusion) and surface lipids (two-dimensional diffusion), the coefficients have been scaled with , where  is the dimension of the fit (either two or three).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2965744&req=5

pcbi-1000964-g006: Diffusion coefficients of the lipid components.Each point in the plot describes the diffusion coefficient for one of the lipid types. The distance is the average distance of the given lipid from the COM of the particle. To facilitate comparison between core (three-dimensional diffusion) and surface lipids (two-dimensional diffusion), the coefficients have been scaled with , where is the dimension of the fit (either two or three).
Mentions: Figure 6 depicts how the diffusion rate varies significantly inside the lipid droplet and/or full HDL. The diffusion is the slowest in the middle of the particle, it speeds up as the molecules get closer to the interface, and the fastest diffusion is found at the interface. The influence of apoA-I on diffusion of lipids is modest. It turns out that the lipid diffusion coefficients in the protein-free lipid droplet and the full HDL particle are almost similar. The apoA-I proteins may slow down the diffusion of lipids slightly especially close to the interfacial regions. The effect is, however, weak (see Table 2).

Bottom Line: Yet, not only the conformations but also the dynamics of lipids are found to be distinctly different in the different regions of HDL, highlighting the importance of dynamics in considering the functionalization of HDL.Our results reveal that not only hydrophobicity but also conformational entropy of the molecules are the driving forces in the formation of HDL structure.The results provide the first detailed structural model for HDL and its dynamics with and without apoA-I, and indicate how the interplay and competition between entropy and detailed interactions may be used in nanoparticle and drug design through self-assembly.

View Article: PubMed Central - PubMed

Affiliation: Department of Physics, Tampere University of Technology, Tampere, Finland.

ABSTRACT
We study the structure and dynamics of spherical high density lipoprotein (HDL) particles through coarse-grained multi-microsecond molecular dynamics simulations. We simulate both a lipid droplet without the apolipoprotein A-I (apoA-I) and the full HDL particle including two apoA-I molecules surrounding the lipid compartment. The present models are the first ones among computational studies where the size and lipid composition of HDL are realistic, corresponding to human serum HDL. We focus on the role of lipids in HDL structure and dynamics. Particular attention is paid to the assembly of lipids and the influence of lipid-protein interactions on HDL properties. We find that the properties of lipids depend significantly on their location in the particle (core, intermediate region, surface). Unlike the hydrophobic core, the intermediate and surface regions are characterized by prominent conformational lipid order. Yet, not only the conformations but also the dynamics of lipids are found to be distinctly different in the different regions of HDL, highlighting the importance of dynamics in considering the functionalization of HDL. The structure of the lipid droplet close to the HDL-water interface is altered by the presence of apoA-Is, with most prominent changes being observed for cholesterol and polar lipids. For cholesterol, slow trafficking between the surface layer and the regimes underneath is observed. The lipid-protein interactions are strongest for cholesterol, in particular its interaction with hydrophobic residues of apoA-I. Our results reveal that not only hydrophobicity but also conformational entropy of the molecules are the driving forces in the formation of HDL structure. The results provide the first detailed structural model for HDL and its dynamics with and without apoA-I, and indicate how the interplay and competition between entropy and detailed interactions may be used in nanoparticle and drug design through self-assembly.

Show MeSH