Date/Time
Date(s) - 10/03/2010
3:20 pm - 4:20 pm

Title: Cholesterolâ??s Location In Bilayers May Be Determined By Lipid Composition

Speaker: Dr. John Katsaras – NRC

Institute:

Location: ABB 102

Description:

In biological membranes the lateral sequestration of lipids with polyunsaturated fatty acid (PUFA) chains (e.g., diC20:4PC) into membrane domains depleted of cholesterol has been hypothesized to have an important role in neurological function and in alleviating a number of health related problems. This kind of domain formation may be the result of the strong aversion of disordered PUFA chains to cholesterolâ??s planar rigid surface.
Neutron studies of â??headgroupâ? deuterated cholesterol incorporated into PUFA bilayers has revealed cholesterolâ??s hydroxyl group to reside at the bilayer centre.1 This result was interpreted in terms of cholesterol preferentially sequestering inside the membrane, and in contrast to its usual position, where the hydroxyl group locates near the lipid/water interface. Further neutron scattering experiments using â??tailâ? deuterated cholesterol confirmed that in fact the molecule is laying flat in the bilayers.2 Subsequent molecular dynamics (MD) simulations3 using the MARTINI coarse grained force field found cholesterol undergoing rapid flip-flop between the bilayerâ??s two leaflets, but spending a considerable amount of time in the membraneâ??s interior, in line with the neutron scattering data.
Kučerka et al.4 have recently elucidated cholesterolâ??s preference for different lipids, namely POPC (16:0-18:1 PC) and DMPC (14:0-14:0 PC). By titrating POPC into PUFA bilayers, it was found that it took ~ 50 mol% of POPC to cause cholesterol to revert to its upright orientation, while only 5 mol% of DMPC was needed to achieve the same result. MD simulation data have also shown that DMPC and cholesterol form domains within PUFA bilayers. Experimental evidence promoting the so-called â??umbrellaâ? model of lipid-cholesterol association will be presented.