Principles of self-organization and load adaptation by the actin cytoskeleton during clathrin-mediated endocytosis
Abstract
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.
Data availability
All code associated with simulation and analysis is available at https://github.com/DrubinBarnes/Akamatsu_CME_manuscript .
Article and author information
Author details
Funding
National Institutes of Health (R35GM118149)
- David G Drubin
Arnold and Mabel Beckman Foundation
- Matthew Akamatsu
Human Frontier Science Program (LT000234/2018-L)
- Daniel Serwas
Army Research Office (W911NF1610411)
- Padmini Rangamani
Office of Naval Research (N00014-17-1-2628)
- Padmini Rangamani
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Patricia Bassereau, Institut Curie, France
Version history
- Received: July 2, 2019
- Accepted: January 16, 2020
- Accepted Manuscript published: January 17, 2020 (version 1)
- Accepted Manuscript updated: January 21, 2020 (version 2)
- Version of Record published: February 25, 2020 (version 3)
Copyright
© 2020, Akamatsu et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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