A Rationale for Mesoscopic Domain Formation in Biomembranes.

Nicolas Destainville,Manoel Manghi,Julie Cornet

doi:10.3390/biom8040104

Abstract

Cell plasma membranes display a dramatically rich structural complexity characterized by functional sub-wavelength domains with specific lipid and protein composition. Under favorable experimental conditions, patterned morphologies can also be observed in vitro on model systems such as supported membranes or lipid vesicles. Lipid mixtures separating in liquid-ordered and liquid-disordered phases below a demixing temperature play a pivotal role in this context. Protein-protein and protein-lipid interactions also contribute to membrane shaping by promoting small domains or clusters. Such phase separations displaying characteristic length-scales falling in-between the nanoscopic, molecular scale on the one hand and the macroscopic scale on the other hand, are named mesophases in soft condensed matter physics. In this review, we propose a classification of the diverse mechanisms leading to mesophase separation in biomembranes. We distinguish between mechanisms relying upon equilibrium thermodynamics and those involving out-of-equilibrium mechanisms, notably active membrane recycling. In equilibrium, we especially focus on the many mechanisms that dwell on an up-down symmetry breaking between the upper and lower bilayer leaflets. Symmetry breaking is an ubiquitous mechanism in condensed matter physics at the heart of several important phenomena. In the present case, it can be either spontaneous (domain buckling) or explicit, i.e., due to an external cause (global or local vesicle bending properties). Whenever possible, theoretical predictions and simulation results are confronted to experiments on model systems or living cells, which enables us to identify the most realistic mechanisms from a biological perspective.

Highlights

The plasma membrane, a complex mixture of lipids and proteins, forms a selective barrier for eukaryotic cells [1,2], yet its role goes far beyond a simple frontier delimiting the cell interior and exterior
We especially focus on the many mechanisms that dwell on an up-down symmetry breaking between the upper and lower bilayer leaflets
These models agree on the existence of finite-size domains in the steady state instead of the macrophase that would prevail in equilibrium

Summary

Introduction

The plasma membrane, a complex mixture of lipids and proteins, forms a selective barrier for eukaryotic cells [1,2], yet its role goes far beyond a simple frontier delimiting the cell interior and exterior. In the original 1972 model by Singer and Nicolson [3], the plasma membrane was seen as a more or less homogeneous mixture in which the proteins represent about 50% of the total mass. Since this model has known regular improvements, leading to the deciphering of an increasing organizational complexity, notably at the sub-micron level, and a growing understanding of the biophysical and biochemical mechanisms at play [4,5,6,7,8,9,10]. The membrane is made up of a lipid bilayer (mainly phospholipids, sphingolipids and cholesterol), the arrangement of which minimizes contact between water and the hydrophobic tails of these amphiphilic molecules [11].

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