Structure and organization in inclusion-containing bilayer membranes

TL;DR

This paper presents a theoretical model explaining how inclusions like proteins and nanoparticles influence membrane structure, organization, and phase behavior, revealing mechanisms behind raft formation, chaining, and layering transitions in bilayer membranes.

Contribution

It introduces a general model system for inclusion-containing bilayer membranes that unifies experimental observations and explains the effects of inclusions on membrane heterogeneity and organization.

Findings

Lipid/inclusion-rich raft domains form at moderate inclusion levels.

High inclusion content leads to chaining of inclusions due to lipid-mediated attraction.

Inclusions cause membrane thickening and layering transitions from one to two layers.

Abstract

Membrane organization is essential for cellular functions such as signal transduction and membrane trafficking. A major challenge is to understand the lateral heterogeneous structures in membranes and membrane fluidity in the presence of inclusions. Based on a considerable amount of experimental evidence for lateral organization of lipid membranes which share astonishingly similar features in the presence of different inclusions, we first present a general model system of bilayer membranes embedded by nanosized inclusions, and explain experimental findings. Here, the hydrophobic inclusions are simple models of intrinsic membrane proteins, cholesterol embedded in the membrane, hydrophobic drugs, or other nanoparticles for bio-medical applications. It is found that lipid/inclusion-rich raft domains are formed at moderate inclusion concentrations, and disappear with the increase of inclusions. At high inclusion content, chaining of inclusions occurs due to the effective attraction between inclusions mediated by lipids. Meanwhile, increasing inclusions can also cause thickening of the membrane, and the distribution of inclusions undergoes a layering transition from one-layer located in the bilayer midplane to two-layer structure arranged into the two leaflets of a bilayer. Our theoretical predictions address the complex interactions between membranes and inclusions, suggesting a unifying mechanism which reflects the competition between the conformational entropy of lipids favoring the formation of lipid-rich rafts and the steric repulsion of inclusions leading to the uniform dispersion.