Noninvasisve Neutron Scattering Measurements Reveal Slower Cholesterol Transport in Model Lipid Membranes
S. Garg, Lionel Porcar, Paul Butler, U. Perez-Salas, A. C. Woodka
Proper cholesterol transport is essential to healthy cellular activity and any abnormality can lead to several fatal diseases. However, a complete understanding of cholesterol homeostasis in the cell remains elusive. Among other things, research in this field has been hampered by a wide range of reported values for intra- and inter-membrane cholesterol transport rates. A possible source for these discrepancies is the technical limitations of available methodologies which usually employ extraneous compounds and chemical tags that might affect the transport rate measurements. To overcome such limitations, this work utilized the Time Resolved Small Angle Neutron Scattering technique to measure cholesterol inter-membrane exchange and intra-membrane flipping rates in-situ without recourse to any external fields or compounds. Overall, the transfer rates of cholesterol in POPC lipid membranes were found to be slower than most values reported in the literature with the most accentuated values for flipping rates. In addition, replacement of cholesterol with DHE (florescent cholesterol analogue) or the addition of 2 mM cyclodextrine are shown to significantly accelerate not only the cholesterol exchange rates (expected for cyclodextrin) but also the flipping rates. These results demonstrate the dramatic effect of commonly used compounds on the cholesterol transport kinetics as well as the power of time resolved SANS with contrast matching to help unravel the details of the transport mechanisms in these complex systems.
Proceedings of the National Academy of Sciences of the United States of America
Cholesterol transport, lipid, biomembrane, time-resolved SANS
, Porcar, L.
, Butler, P.
, Perez-Salas, U.
and Woodka, A.
Noninvasisve Neutron Scattering Measurements Reveal Slower Cholesterol Transport in Model Lipid Membranes, Proceedings of the National Academy of Sciences of the United States of America, [online], https://tsapps.nist.gov/publication/get_pdf.cfm?pub_id=906610
(Accessed December 3, 2023)