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

March 2017

Lipid composition of human low-density lipoprotein (LDL) and its physicochemical characteristics are relevant for proper functioning of lipid transport in blood circulation. The interaction of the proteins forming the surface of lipoproteins determines whether triglycerides and cholesterol will be added to or removed from the lipoprotein transport particles. According to these two functionalities, the common use is to distinguish between “bad” and “good” cholesterol when designating LDL and high density lipoproteins (HDL) although both are essential in certain quantities for the correct functioning.

To explore dynamical and structural features of LDL particles with either a normal or a triglyceride-rich lipid composition, which can be used to mimic the pathological state of a hyperlipidemic patient, we combined coherent and incoherent neutron scattering methods. The investigations were carried out under high hydrostatic pressure (HHP) to study the physicochemical behavior of biomolecules in solution at a molecular level. With both neutron techniques, we applied HHP to probe the shape and degree of freedom of the possible motions (in 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 fraction 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.

These results have been published in www.nature.com/articles/srep46034.

Contact: Dr J. Peters, ILL