Effects of Lipid Composition on Bilayer Membranes Quantified by All-Atom Molecular Dynamics.

Wei Ding,Michail Palaiokostas,Wen Wang,Mario Orsi

doi:10.1021/acs.jpcb.5b06604

Wei Ding, Michail Palaiokostas + Show 2 more

Open Access

https://doi.org/10.1021/acs.jpcb.5b06604

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Abstract

Biological bilayer membranes typically contain varying amounts of lamellar and nonlamellar lipids. Lamellar lipids, such as dioleoylphosphatidylcholine (DOPC), are defined by their tendency to form the lamellar phase, ubiquitous in biology. Nonlamellar lipids, such as dioleoylphosphatidylethanolamine (DOPE), prefer instead to form nonlamellar phases, which are mostly nonbiological. However, nonlamellar lipids mix with lamellar lipids in biomembrane structures that remain overall lamellar. Importantly, changes in the lamellar vs nonlamellar lipid composition are believed to affect membrane function and modulate membrane proteins. In this work, we employ atomistic molecular dynamics simulations to quantify how a range of bilayer properties are altered by variations in the lamellar vs nonlamellar lipid composition. Specifically, we simulate five DOPC/DOPE bilayers at mixing ratios of 1/0, 3/1, 1/1, 1/3, and 0/1. We examine properties including lipid area and bilayer thickness, as well as the transmembrane profiles of electron density, lateral pressure, electric field, and dipole potential. While the bilayer structure is only marginally altered by lipid composition changes, dramatic effects are observed for the lateral pressure, electric field, and dipole potential profiles. Possible implications for membrane function are discussed.

Highlights

The lipid bilayer plays many key structural and functional roles within biological membranes.[1]
The calculated area per lipid (AL), volume per lipid (VL) and the bilayer thickness of the simulated systems are shown in Figure 2, together with available literature data from experiments and from simulations of the same all-atom force field used in this work
This study presented a computational investigation into how a number of physical properties of lipid bilayer membranes are affected by changes in the lipid composition

Summary

Introduction

The lipid bilayer plays many key structural and functional roles within biological membranes.[1] For example, it envelops cells, compartmentalizes the intracellular space, and acts as a selective barrier to permeation. A detailed understanding of the properties of lipid bilayers is central to biology, and is relevant to many applications in the medical and pharmaceutical fields, ranging from biosensors[2,3] to drug design and delivery.[4−6] the current knowledge on lipid membranes is limited, especially with respect to molecular-level properties and phenomena. Membrane properties can exhibit significant variations as a function of depth inside the bilayer, yet measuring experimentally such variations can be extremely difficult, because of the membrane’s very small thickness (∼5 nm) compounded by high heterogeneity, disorder, and fluidity. MD has proved to be a powerful tool to study many aspects of biological membranes at the nanoscale.[7−11]

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