Structural organization of sterol molecules in DPPC bilayers: a coarse-grained molecular dynamics investigation

We investigate the structural organization of cholesterol (CHOL) analogues in 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) bilayers using coarse-grained molecular dynamics simulations and the MARTINI forcefield. Different sterol molecules are modelled by increasing (CHOLL) or decreasing (CHOLS) the diameter of the sterol beads employed in the MARTINI model of CHOL. At high sterol concentrations, (x(sterol) = 0.5), typical of liquid ordered phases, we find that the sterol arrangement and sterol-DPPC interactions strongly depend on the sterol size. Smaller sterols (CHOLS and CHOL) form linear clusters, while the larger sterols (CHOLL) arrange themselves into disc shaped clusters. By combining structural and dynamical properties we also investigate the S-o -> L-d transition for the CHOLL and CHOLS sterols. We show that small changes in the sterol size significantly affect the stability of the gel phase with the gel phase stabilized by the small sterols, but destabilized by large sterols. The general dependence of the phase behaviour of the membrane with sterol content is reminiscent of the one observed in naturally occurring membranes. The relevance of our results to understand current cholesterol-bilayer structural models is discussed.