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.

Reviewing Editor

  1. Aleksandra M Walczak, École Normale Supérieure, France

Version history

  1. Preprint posted: June 24, 2020 (view preprint)
  2. Received: June 24, 2020
  3. Accepted: September 9, 2021
  4. Accepted Manuscript published: September 20, 2021 (version 1)
  5. Version of Record published: September 28, 2021 (version 2)

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.

Metrics

  • 836
    views
  • 122
    downloads
  • 2
    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. 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

Share this article

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

Further reading

    1. Microbiology and Infectious Disease
    2. Physics of Living Systems
    Fabien Duveau, Céline Cordier ... Pascal Hersen
    Research Article

    Natural environments of living organisms are often dynamic and multifactorial, with multiple parameters fluctuating over time. To better understand how cells respond to dynamically interacting factors, we quantified the effects of dual fluctuations of osmotic stress and glucose deprivation on yeast cells using microfluidics and time-lapse microscopy. Strikingly, we observed that cell proliferation, survival, and signaling depend on the phasing of the two periodic stresses. Cells divided faster, survived longer, and showed decreased transcriptional response when fluctuations of hyperosmotic stress and glucose deprivation occurred in phase than when the two stresses occurred alternatively. Therefore, glucose availability regulates yeast responses to dynamic osmotic stress, showcasing the key role of metabolic fluctuations in cellular responses to dynamic stress. We also found that mutants with impaired osmotic stress response were better adapted to alternating stresses than wild-type cells, showing that genetic mechanisms of adaptation to a persistent stress factor can be detrimental under dynamically interacting conditions.

    1. Physics of Living Systems
    Josep-Maria Armengol-Collado, Livio Nicola Carenza, Luca Giomi
    Research Article Updated

    We formulate a hydrodynamic theory of confluent epithelia: i.e. monolayers of epithelial cells adhering to each other without gaps. Taking advantage of recent progresses toward establishing a general hydrodynamic theory of p-atic liquid crystals, we demonstrate that collectively migrating epithelia feature both nematic (i.e. p = 2) and hexatic (i.e. p = 6) orders, with the former being dominant at large and the latter at small length scales. Such a remarkable multiscale liquid crystal order leaves a distinct signature in the system’s structure factor, which exhibits two different power-law scaling regimes, reflecting both the hexagonal geometry of small cells clusters and the uniaxial structure of the global cellular flow. We support these analytical predictions with two different cell-resolved models of epithelia – i.e. the self-propelled Voronoi model and the multiphase field model – and highlight how momentum dissipation and noise influence the range of fluctuations at small length scales, thereby affecting the degree of cooperativity between cells. Our construction provides a theoretical framework to conceptualize the recent observation of multiscale order in layers of Madin–Darby canine kidney cells and pave the way for further theoretical developments.