A circular zone of attachment to the extracellular matrix provides directionality to the motility of Toxoplasma gondii in 3D

  1. Rachel V Stadler
  2. Shane R Nelson
  3. David M Warshaw
  4. Gary E Ward  Is a corresponding author
  1. University of Vermont, United States
  2. University of Vermont Larner College of Medicine, United States

Abstract

Toxoplasma gondii is a protozoan parasite that infects 30-40% of the world's population. Infections are typically subclinical but can be severe and, in some cases, life threatening. Central to the virulence of T. gondii is an unusual form of substrate-dependent motility that enables the parasite to invade cells of its host and to disseminate throughout the body. A hetero-oligomeric complex of proteins that functions in motility has been characterized, but how these proteins work together to drive forward motion of the parasite remains controversial. A key piece of information needed to understand the underlying mechanism(s) is the directionality of the forces that a moving parasite exerts on the external environment. The linear motor model of motility, which has dominated the field for the past two decades, predicts continuous anterior-to-posterior force generation along the length of the parasite. We show here using three-dimensional traction force mapping that the predominant forces exerted by a moving parasite are instead periodic and directed in towards the parasite at a fixed circular location within the extracellular matrix. These highly localized forces, which are generated by the parasite pulling on the matrix, create a visible constriction in the parasite’s plasma membrane. We propose that the ring of inward-directed force corresponds to a circumferential attachment zone between the parasite and the matrix, through which the parasite propels itself to move forward. The combined data suggest a closer connection between the mechanisms underlying parasite motility and host cell invasion than previously recognized. In parasites lacking the major surface adhesin, TgMIC2, neither the inward-directed forces nor the constriction of the parasite membrane are observed. The trajectories of the TgMIC2-deficient parasites are less straight than those of wild-type parasites, suggesting that the annular zone of TgMIC2-mediated attachment to the extracellular matrix normally constrains the directional options available to the parasite as it migrates through its surrounding environment.

Data availability

The FIDVC code used for the 3D force mapping is freely available through github (https://github.com/FranckLab/FIDVC).

Article and author information

Author details

  1. Rachel V Stadler

    Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1049-1638
  2. Shane R Nelson

    Department of Molecular Physiology and Biophysics, University of Vermont, Burlington, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. David M Warshaw

    Department of Molecular Physiology and Biophysics, University of Vermont, Burlington, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Gary E Ward

    Deaprtment of Microbiology and Molecular Genetics, University of Vermont Larner College of Medicine, Burlington, United States
    For correspondence
    Gary.Ward@uvm.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4138-3055

Funding

National Institute of Allergy and Infectious Diseases (AI139201)

  • Gary E Ward

National Institute of Allergy and Infectious Diseases (AI137767)

  • Gary E Ward

National Institute of General Medical Sciences (GM141743)

  • David M Warshaw

National Institute of General Medical Sciences (S10OD026884)

  • David M Warshaw

National Institute of Allergy and Infectious Diseases (T32AI055402)

  • Rachel V Stadler

National Institute of Allergy and Infectious Diseases (F31AI145214)

  • Rachel V Stadler

American Heart Association (19PRE34370071)

  • Rachel V Stadler

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Dominique Soldati-Favre, University of Geneva, Switzerland

Version history

  1. Preprint posted: June 9, 2022 (view preprint)
  2. Received: November 25, 2022
  3. Accepted: November 29, 2022
  4. Accepted Manuscript published: December 15, 2022 (version 1)
  5. Version of Record published: January 13, 2023 (version 2)

Copyright

© 2022, Stadler 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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  1. Rachel V Stadler
  2. Shane R Nelson
  3. David M Warshaw
  4. Gary E Ward
(2022)
A circular zone of attachment to the extracellular matrix provides directionality to the motility of Toxoplasma gondii in 3D
eLife 11:e85171.
https://doi.org/10.7554/eLife.85171

Share this article

https://doi.org/10.7554/eLife.85171

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