Glycocalyx is a layer of glycolipids and glycoproteins on the surface of various cell types, which functions in cell–cell recognition, communication and adhesion. Shurer et al. show that the glycoproteins of the glycocalyx also have the capacity to shape the plasma membrane.

Credit: V. Summersby/Springer Nature Limited

Important components of the glycocalyx are mucins — transmembrane, elongated and flexible glycoprotein polymers that extend from the cell surface. Overexpression of mucins in epithelial cells resulted in the emergence of tubular plasma membrane projections. Such membrane tubulation was not observed following overexpression of rigid glycoproteins and could be reversed by removing mucins from the cell surface. Furthermore, mucins could bend synthetic membranes in vitro. Thus, mucins induce membrane bending and tubulation, which rely on their molecular flexibility.

The extent of membrane tubulation correlated with the levels of mucin expression, both in epithelial cells overexpressing mucins and in human carcinoma cell lines, which are known to upregulate mucin expression. At higher levels of expression, mucins acquired more extended conformations, suggesting that the repulsion between the polymer chains resulting from their crowding is the source of free energy for membrane bending.

Tubules formed by mucin overexpression typically contained an F-actin core. Disruption of F-actin assembly led to the emergence of undulating membrane protrusions harbouring multiple pearl-like structures, which could undergo spontaneous fission to generate extracellular vesicles. Medium isolated from mucin-overexpressing epithelial cells contained large amounts of extracellular vesicles. Higher propensity for generating extracellular vesicles correlated with mucin expression also in human carcinoma cells. Thus, membrane protrusions induced by the glycocalyx can serve as a source of extracellular vesicles following the disassembly of their F-actin core.

mucins induce membrane bending and tubulation

In the future, it will be interesting to study the importance and implications of glycocalyx-induced membrane shaping in different cellular contexts. Specifically, in light of the frequent changes in the glycocalyx associated with tumorigenesis, these studies could provide new insights into cancer development.