Membrane bending: the power of protein imbalance

• Proteins in a lipid bilayer collide like a 2D gas.
• Collisions that occur on one side of the membrane drive membrane deformation.
• Crowding of cargoes with large luminal domains impedes COPII vesicle formation.
• Protein crowding may have a positive effect in other membrane deformation events.

Many cellular processes require membrane deformation, which is driven by specialized protein machinery and can often be recapitulated using pure lipid bilayers. However, biological membranes contain a large amount of embedded proteins. Recent research suggests that membrane-bound proteins with asymmetric distribution of mass across the bilayer can influence membrane bending in a nonspecific manner due to molecular crowding. This mechanism is physical in nature and arises from collisions between such ‘mushroom-shaped’ proteins. It can either facilitate or impede the action of protein coats, for example COPII, during vesicle budding. We describe the physics of how molecular crowding can influence membrane bending and discuss the implications for other cellular processes, such as sorting of glycosylphosphatidylinositol-anchored proteins (GPI-APs) and production of intraluminal vesicles.