Force generation by actin assembly shapes cellular membranes. The mechanisms that govern the organization of cytoskeletal complexes to produce directional force in cells are not understood, particularly in the localized membrane deformations required for membrane trafficking. An experimentally constrained multiscale model shows that a minimal branched actin network is sufficient to internalize endocytic pits against membrane tension. Around 200 activated Arp2/3 complexes are required for robust internalization. A newly developed molecule-counting method determined that ~200 Arp2/3 complexes assemble at sites of clathrin-mediated endocytosis in human cells. Simulations predict that actin self-organizes into a radial branched array with growing ends oriented toward the base of the pit. Long actin filaments bend between attachment sites in the coat and the base of the pit. Elastic energy stored in bent filaments, whose presence was confirmed by cryo-electron tomography, contributes to endocytic internalization. Elevated membrane tension directs more growing filaments toward the base of the pit, increasing actin nucleation and bending for increased force production. Thus, spatially constrained actin filament assembly utilizes an adaptive mechanism enabling endocytosis under varying physical constraints. These principles of actin self-organization and load adaptation are likely utilized by a number of endomembrane trafficking processes that deform and exchange membranes in the stochastic cellular environment.
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Self-organization and load adaptation by mammalian endocytic actin networks
University of California, Berkeley | Postdoctoral Research Fellow, Department of Molecular & Cell BiologySeminar date:
Monday, February 1, 2021 - 12:00 to 13:00Location:
Fields of interest: