Abstract
The plasma membrane has a highly asymmetric distribution of lipids and contains dynamic nanodomains many of which are liquid entities surrounded by a second, slightly different, liquid environment. Contributing to the dynamics is a continuous repartitioning of components between the two types of liquids and transient links between lipids and proteins, both to extracellular matrix and cytoplasmic components, that temporarily pin membrane constituents. This make plasma membrane nanodomains exceptionally challenging to study and much of what is known about membrane domains has been deduced from studies on model membranes at equilibrium. However, living cells are by definition not at equilibrium and lipids are distributed asymmetrically with inositol phospholipids, phosphatidylethanolamines and phosphatidylserines confined mostly to the inner leaflet and glyco- and sphingolipids to the outer leaflet. Moreover, each phospholipid group encompasses a wealth of species with different acyl chain combinations whose lateral distribution is heterogeneous. It is becoming increasingly clear that asymmetry and pinning play important roles in plasma membrane nanodomain formation and coupling between the two lipid monolayers. How asymmetry, pinning, and interdigitation contribute to the plasma membrane organization is only beginning to be unraveled and here we discuss their roles and interdependence.
Highlights
Reviewed by: Erdinc Sezgin, University of Oxford, UK Hector Martinez-Seara, Institute of Organic Chemistry and Biochemistry (IOCB) of the CAS, Czechia
This make plasma membrane nanodomains exceptionally challenging to study and much of what is known about membrane domains has been deduced from studies on model membranes at equilibrium
It is becoming increasingly clear that asymmetry and pinning play important roles in plasma membrane nanodomain formation and coupling between the two lipid monolayers
Summary
Already in the early 1970’s it was known that the human erythrocyte membrane displays leaflet asymmetry in the phospholipid composition (Bretscher, 1972; Verkleij et al, 1973) with most phosphatidylcholine (PC) and sphingomyelin (SM) present in the outer leaflet, whereas phosphatidylserine (PS), phosphatidylethanolamine (PE), and phosphatidylinositol (PI) are in the inner leaflet (Figure 1) This architecture has often been regarded as a prototype of the plasma membrane of mammalian cells. The second is the degree of asymmetry: an asymmetric distribution of a particular lipid means that the distribution between the two leaflets is not 50:50 It could be 60:40, but it could be nearly 100:0, and the distribution or any change thereof is likely to influence membrane properties. Using the lipid distribution data from natural membranes, we should be able to generate realistic models to explain the role of the asymmetric lipid distribution in cellular processes taking place in membranes
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