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
N1 - Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
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 - Article
C2 - 31110185
AN - SCOPUS:85066021599
SN - 2045-2322
VL - 9
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 7591
ER -