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High hydrostatic pressure specifically affects molecular dynamics and shape of low-density lipoprotein particles

View Article: PubMed Central - PubMed

ABSTRACT

Lipid composition of human low-density lipoprotein (LDL) and its physicochemical characteristics are relevant for proper functioning of lipid transport in the blood circulation. To explore dynamical and structural features of LDL particles with either a normal or a triglyceride-rich lipid composition we combined coherent and incoherent neutron scattering methods. The investigations were carried out under high hydrostatic pressure (HHP), which is a versatile tool to study the physicochemical behavior of biomolecules in solution at a molecular level. Within both neutron techniques we applied HHP to probe the shape and degree of freedom of the possible motions (within the time windows of 15 and 100 ps) and consequently the flexibility of LDL particles. We found that HHP does not change the types of motion in LDL, but influences the portion of motions participating. Contrary to our assumption that lipoprotein particles, like membranes, are highly sensitive to pressure we determined that LDL copes surprisingly well with high pressure conditions, although the lipid composition, particularly the triglyceride content of the particles, impacts the molecular dynamics and shape arrangement of LDL under pressure.

No MeSH data available.


Sketch of the effect of high hydrostatic pressure on LDL particles (caption see Fig. 1); N-LDL (a) and TG-LDL (b). The blue spring symbolizes the altered dynamics within the particle.
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f8: Sketch of the effect of high hydrostatic pressure on LDL particles (caption see Fig. 1); N-LDL (a) and TG-LDL (b). The blue spring symbolizes the altered dynamics within the particle.

Mentions: The observation that the geometry of the motion changes, with a reduction in the typical confinement size in TG-LDL, could be expected according to Le Chatelier’s principle, saying that compression by HHP will favor a volume reduction and thus lead to reduced dynamics. This behavior was also reflected in the structural data, as shown by SANS. N-LDL appeared slightly elongated and had a discoid shape at the lowest pressure point, whereas TG-LDL was more spherical at the same conditions. Similar characteristics for normolipidemic and triglyceride-rich LDL particles have already been shown with cryo-electron microscopy before3132. At HHP we found that the N-LDL particles did not change their overall shape and stayed in an ellipsoidal conformation. However, the TG-LDL particles adapted their shape from a more spherical to a more elongated form similar to N-LDL (see Fig. 8). In both samples the particle partial molar volume decreased and the surface-to-volume ratio increased with pressure, but the changes were less pronounced for TG-LDL, which on the other hand became deformed. The surface-to-volume ratio change in LDL could be due to differences in the compressibility between shell and core. Other reasons could be a pressure dependent conformational change of the apolipoprotein, which could become more stretched or flat by pressure to cover a larger surface area. Another effect could be a possible lipid phase change induced by pressure or a different equilibrium of unesterified cholesterol between the core and the phospholipid membrane, which could also lead to a different increase in surface-to-volume ratio. We speculate that a combination of several effects might occur. Such variation due to the protein moiety would be in compliance with the dynamical findings which point towards a higher pressure sensitivity of fast local motions within the apoB100 protein or CH2 subgroups.


High hydrostatic pressure specifically affects molecular dynamics and shape of low-density lipoprotein particles
Sketch of the effect of high hydrostatic pressure on LDL particles (caption see Fig. 1); N-LDL (a) and TG-LDL (b). The blue spring symbolizes the altered dynamics within the particle.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5382586&req=5

f8: Sketch of the effect of high hydrostatic pressure on LDL particles (caption see Fig. 1); N-LDL (a) and TG-LDL (b). The blue spring symbolizes the altered dynamics within the particle.
Mentions: The observation that the geometry of the motion changes, with a reduction in the typical confinement size in TG-LDL, could be expected according to Le Chatelier’s principle, saying that compression by HHP will favor a volume reduction and thus lead to reduced dynamics. This behavior was also reflected in the structural data, as shown by SANS. N-LDL appeared slightly elongated and had a discoid shape at the lowest pressure point, whereas TG-LDL was more spherical at the same conditions. Similar characteristics for normolipidemic and triglyceride-rich LDL particles have already been shown with cryo-electron microscopy before3132. At HHP we found that the N-LDL particles did not change their overall shape and stayed in an ellipsoidal conformation. However, the TG-LDL particles adapted their shape from a more spherical to a more elongated form similar to N-LDL (see Fig. 8). In both samples the particle partial molar volume decreased and the surface-to-volume ratio increased with pressure, but the changes were less pronounced for TG-LDL, which on the other hand became deformed. The surface-to-volume ratio change in LDL could be due to differences in the compressibility between shell and core. Other reasons could be a pressure dependent conformational change of the apolipoprotein, which could become more stretched or flat by pressure to cover a larger surface area. Another effect could be a possible lipid phase change induced by pressure or a different equilibrium of unesterified cholesterol between the core and the phospholipid membrane, which could also lead to a different increase in surface-to-volume ratio. We speculate that a combination of several effects might occur. Such variation due to the protein moiety would be in compliance with the dynamical findings which point towards a higher pressure sensitivity of fast local motions within the apoB100 protein or CH2 subgroups.

View Article: PubMed Central - PubMed

ABSTRACT

Lipid composition of human low-density lipoprotein (LDL) and its physicochemical characteristics are relevant for proper functioning of lipid transport in the blood circulation. To explore dynamical and structural features of LDL particles with either a normal or a triglyceride-rich lipid composition we combined coherent and incoherent neutron scattering methods. The investigations were carried out under high hydrostatic pressure (HHP), which is a versatile tool to study the physicochemical behavior of biomolecules in solution at a molecular level. Within both neutron techniques we applied HHP to probe the shape and degree of freedom of the possible motions (within the time windows of 15 and 100 ps) and consequently the flexibility of LDL particles. We found that HHP does not change the types of motion in LDL, but influences the portion of motions participating. Contrary to our assumption that lipoprotein particles, like membranes, are highly sensitive to pressure we determined that LDL copes surprisingly well with high pressure conditions, although the lipid composition, particularly the triglyceride content of the particles, impacts the molecular dynamics and shape arrangement of LDL under pressure.

No MeSH data available.