Principles of self-organization and load adaptation by the actin cytoskeleton during clathrin-mediated endocytosis

• Published in: eLife Vol. 9
• Main Authors: Akamatsu, Matthew, Vasan, Ritvik, Serwas, Daniel, Ferrin, Michael A, Rangamani, Padmini, Drubin, David G
• Format: Journal Article
• Language: English
• Published: England eLife Sciences Publications Ltd 17-01-2020; eLife Sciences Publications, Ltd
• Subjects: Actin; Actin Cytoskeleton - chemistry; Actin Cytoskeleton - metabolism; actin mechanics; Actin-Related Protein 2-3 Complex - chemistry; Actin-Related Protein 2-3 Complex - metabolism; Actins - chemistry; Actins - metabolism; Biomechanical Phenomena - physiology; Cell Biology; Cell Line; Cell Membrane - chemistry; Cell Membrane - metabolism; Cell membranes; Clathrin; Clathrin - chemistry; Clathrin - metabolism; clathrin-mediated endocytosis; cryo-electron tomography; Cytoskeleton; Endocytosis; Endocytosis - physiology; Filaments; human induced pluripotent stem cells; Humans; Induced Pluripotent Stem Cells; Internalization; multiscale modeling; Physics of Living Systems; quantitative microscopy; quantitative microscopy; human induced pluripotent stem cells; cell biology; actin mechanics; multiscale modeling; cryo-electron tomography; human; physics of living systems; clathrin-mediated endocytosis
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.49840

Force generation by actin assembly shapes cellular membranes. 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.