Interleaflet Coupling of Lipid Nanodomains – Insights From in vitro Systems

Abstract

The plasma membrane is a complex system, consisting of two layers of lipids and proteins compartmentalized into small structures called nanodomains. Despite the asymmetric composition of both leaflets, coupling between the layers is surprisingly strong. This can be evidenced, for example, by recent experimental studies performed on phospholipid giant unilamellar vesicles showing that nanodomains formed in the outer layer are perfectly registered with those in the inner leaflet. Similarly, microscopic phase separation in one leaflet can induce phase separation in the opposing leaflet that would otherwise be homogeneous. In this review, we summarize the current theoretical and experimental knowledge that led to the current view that domains areirrespective of their size -commonly registered across the bilayer. Mechanisms inducing registration of nanodomains suggested by theory and calculations are discussed. Furthermore, domain coupling is evidenced by experimental studies based on the sparse number of methods that can resolve registered from independent nanodomains. Finally, implications that those findings using model membrane studies might have for cellular membranes are discussed.

Transbilayer Coupling of Lipids in Cells Investigated by Imaging Fluorescence Correlation Spectroscopy

“…Based upon simulations and model membrane studies, lipid-mediated transbilayer coupling mechanisms have also been proposed 41,42 . The definition of lipid-based transbilayer coupling varies in the literature depending on the context.…”

Regulation of Wnt Signaling Pathways at the Plasma Membrane and Their Misregulation in Cancer

“…The plasma membrane has a complex heterogeneous and highly dynamic structure that is composed of lipids and proteins with varying features and compartmentalized into numerous smaller structures called micro- or nanodomains ( Eggeling et al, 2009 ; Owen et al, 2012 ; Sarmento et al, 2020 ). This heterogeneity leads to formation of ordered membrane domains, also known as lipid rafts or lipid nanodomains, which are assembled from saturated lipids, sphingolipids, sterols, glycolipids, glycoproteins and certain lipid-anchored proteins such as glycosylphosphatidylinositol (GPI)-anchored proteins and fatty acylated proteins, leaving the relatively disordered domains occupied by unsaturated lipids and a large fraction of membrane proteins ( Sezgin et al, 2015 , 2017b ; Fakhree et al, 2019 ; Kusumi et al, 2020 ; Figure 1 ).…”

Organization of gangliosides into membrane nanodomains

“…5) [185]. Mainly registered lipid micro-and nanodomains have been found experimentally [184,185,[197][198][199][200]] and yet the main driving mechanism for the registration of nanodomains is unclear [201]. However, none of these studies addressed directly the coupling of ganglioside nanodomains.…”