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