Crowding at the cellular membranes: Emerging physiological roles and novel study approaches

Cellular membranes are essentially complex and heterogeneous assemblies. The lipid bilayer forms the basis of the membrane architecture, and the associated proteins and surface-exposed glycans, known as glycocalyx, build up a dynamic, highly crowded environment. This intrinsic crowding modulates diffusion within the lipid bilayer, affects the spatial organization of the membrane components, and drives complex membrane morphology. This review addressed several emerging themes, i.e. crowding-induced condensation of intrinsically disordered proteins at the membrane interface and the multifaceted effects of the glycocalyx as a natural crowder at the plasma membrane. We further describe the potential of tailored glycomimetics to enable crowding studies in defined (semi)synthetic systems and molecular sensors as a tool to quantify the dynamics of the membrane-associated crowding.