Spatially Resolving the Condensing Effect of Cholesterol in Lipid Bilayers

We study the effect of cholesterol on the structure of dipalmitoylphosphatidylcholine phospholipid bilayers. Using extensive molecular dynamics computer simulations at atomistic resolution, we observe and quantify several structural changes upon increasing cholesterol content that are collectively known as the condensing effect: a thickening of the bilayer, an increase in lipid tail order, and a decrease in lateral area. We also observe a change in leaflet interdigitation and a lack thereof in the distributions of dipalmitoylphosphatidylcholine headgroup orientations. These results, obtained over a wide range of cholesterol mole fractions, are then used to calibrate the analysis of phosphollpld properties in bilayers containing a single cholesterol molecule per leaflet, which we perform in a spatially resolved way. We find that a single cholesterol molecule affects phosphollplds in its first and second solvation shells, which puts the range of this effective interaction to be on the order of 1-2 nm. We also observe a tendency of phosphollplds to orient their polar headgroups toward the cholesterol, which provides additional support for the umbrella model of bilayer organization.