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

Selma Maric; Tania Kjellerup Lind; Manfred Roman Raida; Eva Bengtsson; Gunilla Nordin Fredrikson; Sarah Rogers; Martine Moulin; Michael Haertlein; V. Trevor Forsyth; Markus R. Wenk; Thomas Günther Pomorski; Thomas Arnebrant; Reidar Lund; Marité Cárdenas

doi:10.1038/s41598-019-43713-6

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

Selma Maric^*, Tania Kjellerup Lind, Manfred Roman Raida, Eva Bengtsson, Gunilla Nordin Fredrikson, Sarah Rogers, Martine Moulin, Michael Haertlein, V. Trevor Forsyth, Markus R. Wenk, Thomas Günther Pomorski, Thomas Arnebrant, Reidar Lund, Marité Cárdenas

^*Corresponding author for this work

Section for Transport Biology

4 Citations (Scopus)

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Abstract

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.

Original language	English
Article number	7591
Journal	Scientific Reports
Volume	9
Pages (from-to)	1-14
ISSN	2045-2322
DOIs	https://doi.org/10.1038/s41598-019-43713-6
Publication status	Published - 2019

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Time-resolved small-angle neutron scattering as a probe for the dynamics of lipid exchange between human lipoproteins and naturally derived membranesFinal published version, 2.63 MBLicence: CC BY

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Maric, S., Lind, T. K., Raida, M. R., Bengtsson, E., Fredrikson, G. N., Rogers, S., Moulin, M., Haertlein, M., Forsyth, V. T., Wenk, M. R., Pomorski, T. G., Arnebrant, T., Lund, R., & Cárdenas, M. (2019). Time-resolved small-angle neutron scattering as a probe for the dynamics of lipid exchange between human lipoproteins and naturally derived membranes. Scientific Reports, 9, 1-14. Article 7591. https://doi.org/10.1038/s41598-019-43713-6

Maric, S, Lind, TK, Raida, MR, Bengtsson, E, Fredrikson, GN, Rogers, S, Moulin, M, Haertlein, M, Forsyth, VT, Wenk, MR, Pomorski, TG, Arnebrant, T, Lund, R & Cárdenas, M 2019, 'Time-resolved small-angle neutron scattering as a probe for the dynamics of lipid exchange between human lipoproteins and naturally derived membranes', Scientific Reports, vol. 9, 7591, pp. 1-14. https://doi.org/10.1038/s41598-019-43713-6

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

abstract = "Atherosclerosis is the main killer in the western world. Today{\textquoteright}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.",

author = "Selma Maric and Lind, {Tania Kjellerup} and Raida, {Manfred Roman} and Eva Bengtsson and Fredrikson, {Gunilla Nordin} and Sarah Rogers and Martine Moulin and Michael Haertlein and Forsyth, {V. Trevor} and Wenk, {Markus R.} and Pomorski, {Thomas G{\"u}nther} and Thomas Arnebrant and Reidar Lund and Marit{\'e} C{\'a}rdenas",

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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

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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.

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

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