Divide and conquer: How phase separation contributes to lateral transport and organization of membrane proteins and lipids

https://doi.org/10.1016/j.chemphyslip.2020.104985Get rights and content

Highlights

  • Lipid demixing can redistribute lipids and proteins into distinct membrane domains.

  • Curvature influences lipid composition and protein spatial distribution in both model and biological systems.

  • Steric, electric, and hydrodynamic forces can redistribute lipids and proteins laterally within membranes.

Abstract

Biological membranes are fluid, dynamic and heterogeneous, with the dual tasks of defining cell compartments and facilitating communication between them. Within membranes, lipid phase separation can alter local composition, dynamics, and allosteric regulation of membrane proteins. The interplay between lipid–lipid, lipid–protein and protein–protein interactions gives flexibility to membrane lateral organization. In this review we examine how lipid phase separation impacts lateral transport of lipids and proteins within membranes. First, we discuss the role of liquid–liquid coexistence in the organization of model biomembranes, and how such demixing can redistribute lipids and proteins into different regions. Next, the role of curvature in membrane patterning via its influence on lipid composition and protein spatial distribution in both model and biological systems is examined. Then, we discuss how critical fluctuations can organize membrane proteins. Finally, we review how external forces can be used to control the organization of lipids and proteins within biomembranes; with examples covering how ATP driven protein adsorption, electrophoresis, and hydrodynamic flow can transport and redistribute lipids and proteins laterally within membranes.

Section snippets

Introduction: biological membranes are complex lipid mixtures

Lipid membranes and the proteins associated with them form many of the interfaces present in cells. Such interfaces facilitate cellular reactions, compartmentalize cytoplasmic contents, and form the barrier between a living cell and its environment. It is challenging to apply the rules of physics and thermodynamics to biological membranes, because their constituent lipid mixtures are complex, dynamic, and maintained in a non-equilibrium state with respect to their composition and spatial

Lipid phase behavior can redistribute proteins

The possibility that liquid–liquid coexistence might occur in biological membranes has generated great excitement because it would be a powerful way to organize proteins and protein–lipid complexes on a microscopic scale. The variation in physical properties between ordered and disordered phases gives them distinct curvature preferences. Asymmetric partitioning of proteins into ordered and disordered phases segregates them in space, alters their dynamics, and influences allosteric signaling.

Lateral reorganization of lipids by proteins and external forces

In model lipid membranes, phase separation has been observed to alter the spatial distribution of membrane proteins, concentrating protein species into distinct micron-scale regions. Such compartmentalization of membrane proteins via phase separation has even been recently observed within living cell membranes (Rayermann et al., 2017). But the influence can also go the other direction: forces exerted by membrane proteins can alter the equilibrium distributions of the surrounding membrane lipids.

Outlook

It remains unexplained why cell membranes contain such lipid diversity and how they control lipid lateral heterogeneity. In particular, due to the technical challenges of observing nanometer-scale changes in lipid composition within living cells, uncertainty remains about whether biological membranes can be said to phase separate. Micron-sized phase separation, visible with an optical microscope, occurs in vacuolar membranes of living yeast cells (Rayermann et al., 2017), and in multiple

Conflict of interest

None declared.

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