Biophysical forces in membrane bending and traffic

Abstract

Intracellular trafficking requires extensive changes in membrane morphology. Cells use several distinct molecular factors and physical cues to remodel membranes. Here, we highlight recent advances in identifying the biophysical mechanisms of membrane curvature generation. In particular, we focus on the cooperation of molecular and physical drivers of membrane bending during three stages of vesiculation: budding, cargo selection, and scission. Taken together, the studies reviewed here emphasize that, rather than a single dominant mechanism, several mechanisms typically work in parallel during each step of membrane remodeling. Important challenges for the future of this field are to understand how multiple mechanisms work together synergistically and how a series of stochastic events can be combined to achieve a deterministic result-assembly of the trafficking vesicle.

Figure 1:. Mechanisms involving membrane curvature that contribute to vesicle biogenesis.

Each stage of vesicle formation likely employs multiple mechanisms that raise the spontaneous curvature of the membrane or that take advantage of this membrane curvature. (a) As the vesicle buds from the membrane, curvature may be generated by the assembly of clathrin, a branched actin network, or crowded disordered proteins. These mechanisms are best understood in the context of endocytic vesicle budding, but likely act at other membrane trafficking routes as well. (b) As cargo is sorted into the nascent vesicle, the shape of transmembrane cargo can result in stronger partitioning into the curved vesicular membrane structure. Cargo size has also been shown to contribute to the morphology of membrane carriers, as is the case for large cargos that drive the formation of tubular COPII vesicles. (c) Finally, scission of membrane trafficking vesicles can involve the polymerization of proteins with a preference of curved membranes, including ESCRT subunits and BAR-domain containing proteins. These protein assemblies can work together with cargo, cytoskeletal networks, and motors to generate the force necessary to drive neck constriction and scission.