Mechanical counterbalance of kinesin and dynein motors in microtubular network regulates cell mechanics, 3D architecture, and mechanosensing

Microtubules (MTs) and MT motor proteins form active 3D networks made of unstretchable cables with rod-like bending mechanics that provide cells with a dynamically changing structural scaffold. In this study, we report an antagonistic mechanical balance within the dynein–kinesin microtubular motor system. Dynein activity drives the microtubular network inward compaction, while isolated activity of kinesins bundles and expands MTs into giant circular bands that deform the cell cortex into discoids. Furthermore, we show that dyneins recruit MTs to sites of cell adhesion, increasing the topographic contact guidance of cells, while kinesins antagonize it via retraction of MTs from sites of cell adhesion. Actin-to-microtubule translocation of septin-9 enhances kinesin–MT interactions, outbalances the activity of kinesins over that of dyneins, and induces the discoid architecture of cells. These orthogonal mechanisms of MT network reorganization highlight the existence of an intricate mechanical balance between motor activities of kinesins and dyneins that controls cell 3D architecture, mechanics, and cell–microenvironment interactions.

This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Nano, copyright © 2021 The Authors. Published by American Chemical Society, after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acsnano.1c04435.

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Work Title Mechanical counterbalance of kinesin and dynein motors in microtubular network regulates cell mechanics, 3D architecture, and mechanosensing
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Open Access
Creators
  1. Alexander S. Zhovmer
  2. Alexis Manning
  3. Chynna Smith
  4. James B. Hayes
  5. Dylan T. Burnette
  6. Jian Wang
  7. Alexander X. Cartagena-Rivera
  8. Nikolay V. Dokholyan
  9. Rakesh K. Singh
  10. Erdem D. Tabdanov
License In Copyright (Rights Reserved)
Work Type Article
Publisher
  1. American Chemical Society (ACS)
Publication Date October 22, 2021
Publisher Identifier (DOI)
  1. 10.1021/acsnano.1c04435
Source
  1. ACS Nano
Deposited June 17, 2022

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Version 1
published

  • Created
  • Added P7 - Revised Post-Print-1.pdf
  • Added Creator Alexander S. Zhovmer
  • Added Creator Alexis Manning
  • Added Creator Chynna Smith
  • Added Creator James B. Hayes
  • Added Creator Dylan T. Burnette
  • Added Creator Jian Wang
  • Added Creator Alexander X. Cartagena-Rivera
  • Added Creator Nikolay V. Dokholyan
  • Added Creator Rakesh K. Singh
  • Added Creator Erdem D. Tabdanov
  • Published
  • Updated Work Title Show Changes
    Work Title
    • Mechanical counterbalance of kinesin and dynein motors in microtubular network regulates cell mechanics, 3D architecture, and mechanosensing
    • ! Mechanical counterbalance of kinesin and dynein motors in microtubular network regulates cell mechanics, 3D architecture, and mechanosensing
  • Updated Work Title Show Changes
    Work Title
    • ! Mechanical counterbalance of kinesin and dynein motors in microtubular network regulates cell mechanics, 3D architecture, and mechanosensing
    • Mechanical counterbalance of kinesin and dynein motors in microtubular network regulates cell mechanics, 3D architecture, and mechanosensing
  • Updated