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

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.

High Hydrostatic Pressure Induces a Lipid Phase Transition and Molecular Rearrangements in Low‐Density Lipoprotein Nanoparticles

“…Third, a characteristic flattening in the overall particle shape can be observed in the front view of all models (Figure ), which correlates with the major diameter changes of the smallest axis D3. The presented results of this ab initio modeling approach roughly reflect the data obtained by fitting an ellipsoidal model to the SANS data of LDL . These earlier data are systematically by 1–3 nm smaller in each dimension, which could be explained by the two completely different approaches, nonetheless, the relations between them are comparable.…”

“…How HHP affects the structure and molecular organization of lipid assemblies composed of a phospholipid monolayer surrounding an oily lipid core, as provided in lipoprotein particles, is not known so far. Only recently, we have reported on the molecular dynamics of lipoproteins under HHP . These data revealed that HHP has a significant impact on the atomic motions and the flexibility of LDL particles, strongly depending on the actual lipid composition.…”

Protein Backbone and Average Particle Dynamics in Reconstituted Discoidal and Spherical HDL Probed by Hydrogen Deuterium Exchange and Elastic Incoherent Neutron Scattering

“…In principle, based on the types of intermolecular interactions within lipids (dispersion) and proteins (Coulomb, H-bond, dispersion), we would expect the lipid domain of HDL to be more dynamic than the protein; but at very lower temperatures (< 200 K), we found that the protein motion dominated the lipid motion in the average particle dynamics, in agreement with earlier findings on natural membranes [66] and purple membranes [67], while at high temperatures (>200 K), the internal dynamics of rHDL exceeded that of rsHDL (given that rHDL had a higher lipid to protein ratio than rsHDL), in agreement with previous results published on other lipoproteins (VLDL and LDL [5][6][7], natural membranes [66], and purple membranes [67]). The inflection points in Figure 1 were chosen somehow arbitrarily according to the variations in the slope, but they allowed to show that the inversion in the tendency between the two samples occurred only at the highest temperature.…”

“…For example, highly dynamic lipoproteins make excellent lipid transporters in the circulatory system. Lipid-containing biomolecules constitute attractive targets for investigation by EINS because their softness and flexibility impact their biological functions, as shown in earlier studies on 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) vesicles [4], very-low-density lipoproteins (VLDL), and low-density lipoproteins (LDL) [5][6][7].…”

Dynamics of a family of cyan fluorescent proteins probed by incoherent neutron scattering

“…The width remains constant over the full Q range ( figure 5); therefore, the corresponding motion is confined and can be described as movement in a sphere with a rotational diffusion coefficient of 0.08 meV. This value is comparable to values found for small rotations of molecular subgroups in deep-sea prokaryotes [45], in neural tissue [46] or in lipoproteins [47]. Such rotational diffusion could originate from different locations in the sample, for instance from protons in CH 2 groups.…”