Issue 42, 2018

Effects of lipid composition on membrane permeation

Abstract

Passive permeation through lipid membranes is an essential process in biology. In vivo membranes typically consist of mixtures of lamellar and nonlamellar lipids. Lamellar lipids are characterized by their tendency to form lamellar sheet-like structures, which are predominant in nature. Nonlamellar lipids, when isolated, instead form more geometrically complex nonlamellar phases. While mixed lamellar/nonlamellar lipid membranes tend to adopt the ubiquitous lamellar bilayer structure, the presence of nonlamellar lipids is known to have profound effects on key membrane properties, such as internal distributions of stress and elastic properties, which in turn may alter related biological processes. This work focuses on one such process, i.e., permeation, by utilising atomistic molecular dynamics simulations in order to obtain transfer free energy profiles, diffusion profiles and permeation coefficients for a series of thirteen small molecules and drugs. Each permeant is tested on two bilayer membranes of different lipid composition, i.e., purely lamellar and mixed lamellar/nonlamellar. Our results indicate that the presence of nonlamellar lipids reduces permeation for smaller molecules (molecular weight < 100) but facilitates it for the largest ones (molecular weight > 100). This work represents an advancement towards the development of more realistic in silico permeability assays, which may have a substantial future impact in the area of rational drug design.

Graphical abstract: Effects of lipid composition on membrane permeation

Supplementary files

Article information

Article type
Paper
Submitted
20 Jun 2018
Accepted
09 Oct 2018
First published
11 Oct 2018

Soft Matter, 2018,14, 8496-8508

Effects of lipid composition on membrane permeation

M. Palaiokostas, W. Ding, G. Shahane and M. Orsi, Soft Matter, 2018, 14, 8496 DOI: 10.1039/C8SM01262H

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements