1. Cell Biology
  2. Physics of Living Systems
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Principles of self-organization and load adaptation by the actin cytoskeleton during clathrin-mediated endocytosis

  1. Matthew Akamatsu
  2. Ritvik Vasan
  3. Daniel Serwas
  4. Michael Alexander Ferrin
  5. Padmini Rangamani  Is a corresponding author
  6. David G Drubin  Is a corresponding author
  1. University of California, Berkeley, United States
  2. University of California, San Diego, United States
  3. University ofCalifornia, Berkeley, United States
Research Article
  • Cited 23
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Cite this article as: eLife 2020;9:e49840 doi: 10.7554/eLife.49840

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

  1. 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.
  2. 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.
  3. 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.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9010-7298
  4. 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.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9899-1169
  5. 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.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5953-4347
  6. 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.
    ORCID icon "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.

Reviewing Editor

  1. Patricia Bassereau, Institut Curie, France

Publication history

  1. Received: July 2, 2019
  2. Accepted: January 16, 2020
  3. Accepted Manuscript published: January 17, 2020 (version 1)
  4. Accepted Manuscript updated: January 21, 2020 (version 2)
  5. 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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