Cyclodextrin mediated cholesterol extraction

It is well known that cyclodextrins (CDs), and especially beta-cyclodextrins, are able to modify the cholesterol concentration in membranes; either in situ (e.g. model membranes) or in vivo (cells). Combining full atomistic resolution with models derived from the MARTINI carbohydrate coarse-grained force field [1], we have been able to dissect the molecular mechanism and reveal the extraction process [2,3]. Our results show that cholesterol can be extracted efficiently upon adsorption of beta-CD dimers at the membrane/water interface. However, extraction is only observed to occur spontaneously in membranes with high cholesterol levels. Comparing lipid/cholesterol compositions typical of liquid-disordered (Ld) and liquid-order (Lo) domains, we furthermore show that cholesterol is preferentially extracted from the disordered regions. Results of this kind of simulations may help to rationalize the design of more efficient CDs in numerous applications.

Related work has addressed the mechanism by which amylose can fold in the presence of lipids, forming inclusion complexes [4]. Currently we study the fascinating interplay between mono and disaccharides with multi-component lipid membranes.

1. C.A. Lopez, A. Rzepiela, A.H. de Vries, L. Dijkhuizen, P.H. Huenenberger, S.J. Marrink. The Martini coarse grained force field: extension to carbohydrates. J. Chem. Th. Comp., 5:3195-3210, 2009.
2. C.A. Lopez, A.H. de Vries, S.J. Marrink. Molecular mechanism of cyclodextrin mediated cholesterol extraction. PLoS Comp. Biol., 7:e1002020, 2011. Open Access
3. C.A. Lopez, A.H. de Vries, S.J. Marrink. Computational microscopy of cyclodextrin mediated cholesterol extraction from lipid model membranes. Sci. Rep., 2013, accepted.
4. C.A. Lopez, A.H. de Vries, S.J. Marrink. Amylose folding under the influence of lipids. Carboh. Res., 364:1-7, 2012.

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