The principal structure of animal plasma membranes is a bilayer formed by numerous types of phospholipids and cholesterol. Such complex mixtures exhibit a staggering range of physical behavior. A systematic approach to elucidate the properties of such multi-component bilayers starts with the simplest possible mixture: a bilayer that contains only a single type of phospholipid as well as cholesterol. Even these comparatively simple, binary mixtures show remarkable behavior. For example, the well-known condensing effect: as the cholesterol content increases, so does the average membrane thickness, while the average area per molecule decreases.
The condensing effect is caused by changes in the ordering of the phospholipids’ alkyl tails, induced by the need to accommodate the rigid cholesterol molecules. This alone can yield surprising results: for example, the area of a membrane might decrease when a cholesterol molecule is added to it. To study this and other effects related to the structure of binary lipid systems, we report in the December 4 issue of the Biophysical Journal the results of atomistic computer simulations that provide us with a detailed view and a statistical sampling of the molecular arrangements in these systems.
However, it is not only the lipids’ tails that respond to the presence of cholesterol. A long-standing model for the spatial organization of multi-component membranes posits that phospholipids will orient their zwitterionic head groups in such a way that they shield a nearby cholesterol molecule from the aqueous solvent, thereby minimizing unfavorable interactions between the hydrophobic cholesterol body and water. Our simulations show that this is indeed the case, as illustrated in the accompanying cover image: a phospholipid (purple) extends its polar head over an adjacent cholesterol molecule (white, with its small polar hydroxyl group shown in red). This behavior, captured here in a single simulation snapshot, manifests itself in a systematic bias in the phospholipids’ head group orientation.
This image demonstrates how computer simulations can be used to shed light on the complex spatial arrangements that emerge in interacting systems. For additional background information and other examples for modeling and simulation of biophysical systems, please visit our website, http://depts.washington.edu/mbmgrp.
- Felix Leeb and Lutz Maibaum