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

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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. 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

Matthew Akamatsu

Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States

Competing interests
The authors declare that no competing interests exist.
Ritvik Vasan

Department of Mechanical and Aerospace Engineering, University of California, San Diego, La Jolla, United States

Competing interests
The authors declare that no competing interests exist.
Daniel Serwas

Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-9010-7298
Michael Alexander Ferrin

Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-9899-1169
Padmini Rangamani

Department of Mechanical and Aerospace Engineering, University of California, San Diego, La Jolla, United States

For correspondence
padmini.rangamani@eng.ucsd.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-5953-4347
David G Drubin

Department of Molecular and Cell Biology, University ofCalifornia, Berkeley, Berkeley, United States

For correspondence
drubin@berkeley.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-3002-6271

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.

Copyright

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.