Condensation tendency and planar isotropic actin gradient induce radial alignment in confined monolayers

  1. Tianfa Xie
  2. Sarah R St Pierre
  3. Nonthakorn Olaranont
  4. Lauren E Brown
  5. Min Wu  Is a corresponding author
  6. Yubing Sun  Is a corresponding author
  1. University of Massachusetts, United States
  2. Worcester Polytechnic Institute, United States

Abstract

A monolayer of highly motile cells can establish long-range orientational order, which can be explained by hydrodynamic theory of active gels and fluids. However, it is less clear how cell shape changes and rearrangement are governed when the monolayer is in mechanical equilibrium states when cell motility diminishes. In this work, we report that rat embryonic fibroblasts (REF), when confined in circular mesoscale patterns on rigid substrates, can transition from the spindle shapes to more compact morphologies. Cells align radially only at the pattern boundary when they are in the mechanical equilibrium. This radial alignment disappears when cell contractility or cell-cell adhesion is reduced. Unlike monolayers of spindle-like cells such as NIH-3T3 fibroblasts with minimal intercellular interactions or epithelial cells like Madin-Darby canine kidney (MDCK) with strong cortical actin network, confined REF monolayers present an actin gradient with isotropic meshwork, suggesting the existence of a stiffness gradient. In addition, the REF cells tend to condense on soft substrates, a collective cell behavior we refer to as the 'condensation tendency'. This condensation tendency, together with geometrical confinement, induces tensile prestretch (i.e., an isotropic stretch that causes tissue to contract when released) to the confined monolayer. By developing a Voronoi-cell model, we demonstrate that the combined global tissue prestretch and cell stiffness differential between the inner and boundary cells can sufficiently define the cell radial alignment at the pattern boundary.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. All sequencing data were uploaded to the GEO public repository (https://www.ncbi.nlm.nih.gov/geo/) and were assigned series GSE148155.

The following data sets were generated

Article and author information

Author details

  1. Tianfa Xie

    Mechanical and Industrial Engineering, University of Massachusetts, Amherst, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1332-4373
  2. Sarah R St Pierre

    Mechanical and Industrial Engineering, University of Massachusetts, Amherst, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Nonthakorn Olaranont

    Mathematical Sciences, Worcester Polytechnic Institute, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Lauren E Brown

    Biomedical Engineering, University of Massachusetts, Amherst, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Min Wu

    Department of Mathematical Sciences, Worcester Polytechnic Institute, Worcester, United States
    For correspondence
    mwu2@wpi.edu
    Competing interests
    The authors declare that no competing interests exist.
  6. Yubing Sun

    Mechanical and Industrial Engineering, University of Massachusetts, Amherst, United States
    For correspondence
    ybsun@umass.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6831-3383

Funding

National Science Foundation (CMMI 1662835)

  • Yubing Sun

National Science Foundation (CMMI 1846866)

  • Yubing Sun

National Science Foundation (DMS 2012330)

  • Min Wu

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

Copyright

© 2021, Xie 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. Tianfa Xie
  2. Sarah R St Pierre
  3. Nonthakorn Olaranont
  4. Lauren E Brown
  5. Min Wu
  6. Yubing Sun
(2021)
Condensation tendency and planar isotropic actin gradient induce radial alignment in confined monolayers
eLife 10:e60381.
https://doi.org/10.7554/eLife.60381

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https://doi.org/10.7554/eLife.60381