Cell membranes are composed of phospholipids, sterols, and proteins.

1. Cholesterol transport rates in model membranes S. Garg1, A.C. Woodka2, P.D. Butler2, U. Perez-Salas1,3, L. Porcar4,5 DMR-0944772, DE-AC02-06CH11357 1ANL, 2NCNR, 3University of Illinois at Chicago, 4ILL, 5University of Delaware Dan Neumann, National Institute of Standards and Technology, DMR 0944772 Cell Membrane • The scattering intensity decreases by 50% as cholesterol equilibrates between donor and acceptor vesicles. • Cell membranes are composed of phospholipids, sterols, and proteins. • Phospholipids are the scaffold in which other components are embedded. • Cholesterol insertion is required to establish proper membrane permeability and fluidity. • Additives (Cylcodextrin) or mimics (DHE) significantly change the measured kinetics. Although proper cholesterol transport is essential to healthy cellular activity it is not very well understood. Transfer rates reported in the literature vary from fractions of a second to hours. In many cases the cholesterol is labeled with a fluorescent dye or substituted with a “cholesterol-like” molecule in order to make measurements possible. It turns out that these extraneous compounds can have a tremendous affect on the measured rates. OR? Two vesicle populations are made: cholesterol-rich donor vesicles and cholesterol-free acceptor vesicles. kex Donor: Cholesterol and lipid Acceptor: lipid Using the CHRNS-supported Small Angle Neutron Scattering (SANS) instrument, and contrast matching we are able to measure cholesterol transfer rates without ANY extraneous compounds. • Cholesterol flipping is significantly slower than reported in the literature. • Flipping could be the rate limiting step for transport. • Cholesterol additives and substitutes alter flipping and exchange rates. Nature News doi:10.1038/news.2011.424 S. Garg et. al. Biophys. J. (2011) 101, 370-377