The axonal actin-spectrin lattice acts as a tension buffering shock absorber

  1. Sushil Dubey
  2. Nishita Bhembre
  3. Shivani Bodas
  4. Sukh Veer
  5. Aurnab Ghose
  6. Andrew Callan-Jones  Is a corresponding author
  7. Pramod Pullarkat  Is a corresponding author
  1. Raman Research Institute, India
  2. Indian Institute of Science Education and Research, India
  3. Indian Institute of Science Education and Research, India
  4. Paris Diderot University, France

Abstract

Axons span extreme distances and are subjected to significant stretch deformations during limb movements or sudden head movements, especially during impacts. Yet, axon biomechanics, and its relation to the ultrastructure that allows axons to withstand mechanical stress, is poorly understood. Using a custom developed force apparatus, we demonstrate that chick dorsal root ganglion axons exhibit a tension buffering or strain-softening response, where its steady state elastic modulus decreases with increasing strain. We then explore the contributions from the various cytoskeletal components of the axon to show that the recently discovered membrane-associated actin-spectrin scaffold plays a prominent mechanical role. Finally, using a theoretical model, we argue that the actin-spectrin skeleton acts as an axonal tension buffer by reversibly unfolding repeat domains of the spectrin tetramers to release excess mechanical stress. Our results revise the current view point that microtubules and their associated proteins are the only significant load-bearing elements in axons.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Sushil Dubey

    Soft Condensed Matter Group, Raman Research Institute, Bangalore, India
    Competing interests
    The authors declare that no competing interests exist.
  2. Nishita Bhembre

    Soft Condensed Matter, Raman Research Institute, Bangalore, India
    Competing interests
    The authors declare that no competing interests exist.
  3. Shivani Bodas

    Department of Biology, Indian Institute of Science Education and Research, Pune, India
    Competing interests
    The authors declare that no competing interests exist.
  4. Sukh Veer

    Soft Condensed Matter Group, Raman Research Institute, Bangalore, India
    Competing interests
    The authors declare that no competing interests exist.
  5. Aurnab Ghose

    Biology, Indian Institute of Science Education and Research, Pune, India
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2053-3918
  6. Andrew Callan-Jones

    Laboratory of complex materials systems, Paris Diderot University, Paris, France
    For correspondence
    andrew.callan-jones@univ-paris-diderot.fr
    Competing interests
    The authors declare that no competing interests exist.
  7. Pramod Pullarkat

    Soft Condensed Matter Group, Raman Research Institute, Bangalore, India
    For correspondence
    pramod@rri.res.in
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2716-7575

Funding

Department of Biotechnology , Ministry of Science and Technology (BT/PR13244/GBD/27/245/2009)

  • Pramod Pullarkat

Department of Biotechnology , Ministry of Science and Technology (BT/PR13244/GBD/27/245/2009)

  • Aurnab Ghose

Science and Engineering Research Board (EMR/2016/003730)

  • Aurnab Ghose

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

Copyright

© 2020, Dubey 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.

Metrics

  • 4,655
    views
  • 553
    downloads
  • 50
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Sushil Dubey
  2. Nishita Bhembre
  3. Shivani Bodas
  4. Sukh Veer
  5. Aurnab Ghose
  6. Andrew Callan-Jones
  7. Pramod Pullarkat
(2020)
The axonal actin-spectrin lattice acts as a tension buffering shock absorber
eLife 9:e51772.
https://doi.org/10.7554/eLife.51772

Share this article

https://doi.org/10.7554/eLife.51772

Further reading

    1. Neuroscience
    2. Physics of Living Systems
    Moritz Schloetter, Georg U Maret, Christoph J Kleineidam
    Research Article

    Neurons generate and propagate electrical pulses called action potentials which annihilate on arrival at the axon terminal. We measure the extracellular electric field generated by propagating and annihilating action potentials and find that on annihilation, action potentials expel a local discharge. The discharge at the axon terminal generates an inhomogeneous electric field that immediately influences target neurons and thus provokes ephaptic coupling. Our measurements are quantitatively verified by a powerful analytical model which reveals excitation and inhibition in target neurons, depending on position and morphology of the source-target arrangement. Our model is in full agreement with experimental findings on ephaptic coupling at the well-studied Basket cell-Purkinje cell synapse. It is able to predict ephaptic coupling for any other synaptic geometry as illustrated by a few examples.

    1. Physics of Living Systems
    James E Hammond, Ruth E Baker, Berta Verd
    Research Article

    Vertebrates have evolved great diversity in the number of segments dividing the trunk body, however, the developmental origin of the evolvability of this trait is poorly understood. The number of segments is thought to be determined in embryogenesis as a product of morphogenesis of the pre-somitic mesoderm (PSM) and the periodicity of a molecular oscillator active within the PSM known as the segmentation clock. Here, we explore whether the clock and PSM morphogenesis exhibit developmental modularity, as independent evolution of these two processes may explain the high evolvability of segment number. Using a computational model of the clock and PSM parameterised for zebrafish, we find that the clock is broadly robust to variation in morphogenetic processes such as cell ingression, motility, compaction, and cell division. We show that this robustness is in part determined by the length of the PSM and the strength of phase coupling in the clock. As previous studies report no changes to morphogenesis upon perturbing the clock, we suggest that the clock and morphogenesis of the PSM exhibit developmental modularity.