Spatially Resolving the Condensing Effect of Cholesterol in Lipid Bilayers

TL;DR

This study uses molecular dynamics simulations to analyze how cholesterol influences lipid bilayer structure, revealing local effects within nanometer scales and supporting the umbrella model of bilayer organization.

Contribution

It provides a detailed, spatially resolved analysis of cholesterol's condensing effect and its influence on phospholipid orientation and bilayer properties.

Findings

Cholesterol causes bilayer thickening and increased lipid tail order.

A single cholesterol molecule influences phospholipids within 1-2 nanometers.

Phospholipids tend to orient their head groups toward cholesterol.

Abstract

We study the effect of cholesterol on the structure of dipalmitoylphosphatidylcholine (DPPC) 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 DPPC head group orientations. These results, obtained over a wide range of cholesterol mole fractions, are then used to calibrate the analysis of phospholipid 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 phospholipids in its first and second solvation shells, which puts the range of this interaction to be on the order of one to two nanometers. We also observe a tendency of phospholipids to orient their polar head groups toward the cholesterol, which provides additional support for the umbrella model of bilayer organization.