Time-resolved small-angle neutron scattering as a probe for the dynamics of lipid exchange between human lipoproteins and naturally derived membranes

TY - JOUR

T1 - Time-resolved small-angle neutron scattering as a probe for the dynamics of lipid exchange between human lipoproteins and naturally derived membranes

AU - Maric, Selma

AU - Lind, Tania Kjellerup

AU - Raida, Manfred Roman

AU - Bengtsson, Eva

AU - Fredrikson, Gunilla Nordin

AU - Rogers, Sarah

AU - Moulin, Martine

AU - Haertlein, Michael

AU - Forsyth, V. Trevor

AU - Wenk, Markus R.

AU - Pomorski, Thomas Günther

AU - Arnebrant, Thomas

AU - Lund, Reidar

AU - Cárdenas, Marité

PY - 2019

Y1 - 2019

N2 - Atherosclerosis is the main killer in the western world. Today’s clinical markers include the total level of cholesterol and high-/low-density lipoproteins, which often fails to accurately predict the disease. The relationship between the lipid exchange capacity and lipoprotein structure should explain the extent by which they release or accept lipid cargo and should relate to the risk for developing atherosclerosis. Here, small-angle neutron scattering and tailored deuteration have been used to follow the molecular lipid exchange between human lipoprotein particles and cellular membrane mimics made of natural, “neutron invisible” phosphatidylcholines. We show that lipid exchange occurs via two different processes that include lipid transfer via collision and upon direct particle tethering to the membrane, and that high-density lipoprotein excels at exchanging the human-like unsaturated phosphatidylcholine. By mapping the specific lipid content and level of glycation/oxidation, the mode of action of specific lipoproteins can now be deciphered. This information can prove important for the development of improved diagnostic tools and in the treatment of atherosclerosis.

AB - Atherosclerosis is the main killer in the western world. Today’s clinical markers include the total level of cholesterol and high-/low-density lipoproteins, which often fails to accurately predict the disease. The relationship between the lipid exchange capacity and lipoprotein structure should explain the extent by which they release or accept lipid cargo and should relate to the risk for developing atherosclerosis. Here, small-angle neutron scattering and tailored deuteration have been used to follow the molecular lipid exchange between human lipoprotein particles and cellular membrane mimics made of natural, “neutron invisible” phosphatidylcholines. We show that lipid exchange occurs via two different processes that include lipid transfer via collision and upon direct particle tethering to the membrane, and that high-density lipoprotein excels at exchanging the human-like unsaturated phosphatidylcholine. By mapping the specific lipid content and level of glycation/oxidation, the mode of action of specific lipoproteins can now be deciphered. This information can prove important for the development of improved diagnostic tools and in the treatment of atherosclerosis.

UR - http://www.scopus.com/inward/record.url?scp=85066021599&partnerID=8YFLogxK

U2 - 10.1038/s41598-019-43713-6

DO - 10.1038/s41598-019-43713-6

M3 - Journal article

C2 - 31110185

AN - SCOPUS:85066021599

SN - 2045-2322

VL - 9

SP - 1

EP - 14

JO - Scientific Reports

JF - Scientific Reports

M1 - 7591

ER -