The disease atherosclerosis is the leading cause of death in the western world; it occurs when plaques accumulate in blood vessels, which can lead to the hardening of arteries and eventually heart disease and stroke. There are several lipoproteins present that transport cholesterol through the blood plasma: amongst them high-density lipoprotein (HDL) and low-density lipoprotein (LDL) are used as biomarkers, and understanding their mechanism is likely to inform the understanding and treatment of the disease.
The accuracy of using the total amount of HDL and LDL in the blood as a predictor of atherosclerosis is low. Therefore, to understand the role that HDL and LDL play in the build-up of arterial plaques, their lipid exchange with the cellular membranes lining the artery wall need to be carefully studied. This study uses selective deuteration, in combination with time-resolved small angle neutron scattering (TR-SANS), to investigate the molecular lipid exchange between human lipoprotein particles and model cell membranes.
The TR-SANS experiments suggest a multi-action mechanism for lipid exchange that includes diffusion, collision and tethering, leading to novel insights into the roles of different molecules present in the lipoprotein particle. The development of this method provides the research community with a way to begin to understand the molecular mechanisms underlying plaque build-up and therefore the onset of atherosclerosis. With developments in deuteration science, it could also lead to systematic study of other complex biological protein-lipid systems.
Related publication: “Time-resolved small-angle neutron scattering as a probe for the dynamics of lipid exchange between human lipoproteins and naturally derived membranes.” Sci Rep 9, 7591 (2019)
Funding: Swedish Research Council, ESS & MAX IV: Cross Border Science and Society and the UNIK research initiative of the Danish Ministry of Science, Technology and Innovation.
Authors: S Maric, TK Lind (Malmö University), MR Raida (National University of Singapore), E Bengtsson, GN Fredrikson (Lund University), S Rogers (ISIS), M Moulin, M Haertlein (ILL), VT Forsyth (ILL, Keele University), MR Wenk (National University of Singapore), TG Pomorski (University of Copenhagen, Ruhr University Bochum), T Arnebrant (Malmö University), R Lund (University of Oslo), M Cárdenas (Malmö University)