Modulation and dynamics of cell membrane heterogeneities

Numerous studies provide evidence that the lipid bilayer of the plasma membrane contains lateral nanodomains, and that these are functionally important regulators of transmembrane cell signaling. Depending on their chemical composition and the biophysical mechanism bringing the lipids together, multiple types of nanodomains exist in the inner and the outer leaflet of the plasma membrane bilayer. In intact cells, these domains are smaller than the optical resolution limit of light microscopy and also highly dynamic. Recently, advanced fluorescence methods have provided data to characterize many biophysical and thermodynamic aspects of these nanodomains. In this review, we summarize the physicochemical determinants of nanodomain formation, stability and extent. Then, we detail how these nanodomains play a structural role by anchoring nucleation sites for the membrane cytoskeleton on the lipid bilayer. Further, we review the existing literature on mechanisms that modulate the nanodomain size and stability, both acute and chronic events. We conclude that regulation of the nanodomains distribution in the lipid bilayer of the plasma membrane is important for modulation of transmembrane signaling. However, only very few modulators of nanodomain stability and size have been quantified in cells, suggesting interesting directions for future studies.