IDEAS home Printed from https://ideas.repec.org/a/plo/pone00/0111803.html
   My bibliography  Save this article

A Mathematical Model for Eph/Ephrin-Directed Segregation of Intermingled Cells

Author

Listed:
  • Rotem Aharon
  • Peter W Janes
  • Anthony W Burgess
  • Kais Hamza
  • Fima Klebaner
  • Martin Lackmann

Abstract

Eph receptors, the largest family of receptor tyrosine kinases, control cell-cell adhesion/de-adhesion, cell morphology and cell positioning through interaction with cell surface ephrin ligands. Bi-directional signalling from the Eph and ephrin complexes on interacting cells have a significant role in controlling normal tissue development and oncogenic tissue patterning. Eph-mediated tissue patterning is based on the fine-tuned balance of adhesion and de-adhesion reactions between distinct Eph- and ephrin-expressing cell populations, and adhesion within like populations (expressing either Eph or ephrin). Here we develop a stochastic, Lagrangian model that is based on Eph/ephrin biology: incorporating independent Brownian motion to describe cell movement and a deterministic term (the drift term) to represent repulsive and adhesive interactions between neighbouring cells. Comparison between the experimental and computer simulated Eph/ephrin cell patterning events shows that the model recapitulates the dynamics of cell-cell segregation and cell cluster formation. Moreover, by modulating the term for Eph/ephrin-mediated repulsion, the model can be tuned to match the actual behaviour of cells with different levels of Eph expression or activity. Together the results of our experiments and modelling suggest that the complexity of Eph/ephrin signalling mechanisms that control cell-cell interactions can be described well by a mathematical model with a single term balancing adhesion and de-adhesion between interacting cells. This model allows reliable prediction of Eph/ephrin-dependent control of cell patterning behaviour.

Suggested Citation

  • Rotem Aharon & Peter W Janes & Anthony W Burgess & Kais Hamza & Fima Klebaner & Martin Lackmann, 2014. "A Mathematical Model for Eph/Ephrin-Directed Segregation of Intermingled Cells," PLOS ONE, Public Library of Science, vol. 9(12), pages 1-19, December.
    • Handle: RePEc:plo:pone00:0111803
    DOI: 10.1371/journal.pone.0111803
    as

    Download full text from publisher

    File URL: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0111803
    Download Restriction: no
    File URL: https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0111803&type=printable
    Download Restriction: no
    File URL: https://libkey.io/10.1371/journal.pone.0111803?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Michaël Reber & Patrick Burrola & Greg Lemke, 2004. "A relative signalling model for the formation of a topographic neural map," Nature, Nature, vol. 431(7010), pages 847-853, October.
    2. Georg Mellitzer & Qiling Xu & David G. Wilkinson, 1999. "Eph receptors and ephrins restrict cell intermingling and communication," Nature, Nature, vol. 400(6739), pages 77-81, July.
    3. Simpson, Matthew J. & Landman, Kerry A. & Hughes, Barry D. & Fernando, Anthony E., 2010. "A model for mesoscale patterns in motile populations," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 389(7), pages 1412-1424.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Baker, Ruth E. & Simpson, Matthew J., 2012. "Models of collective cell motion for cell populations with different aspect ratio: Diffusion, proliferation and travelling waves," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 391(14), pages 3729-3750.
    2. Jonas Stewen & Kai Kruse & Anca T. Godoi-Filip & Zenia & Hyun-Woo Jeong & Susanne Adams & Frank Berkenfeld & Martin Stehling & Kristy Red-Horse & Ralf H. Adams & Mara E. Pitulescu, 2024. "Eph-ephrin signaling couples endothelial cell sorting and arterial specification," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    3. David C Sterratt & Daniel Lyngholm & David J Willshaw & Ian D Thompson, 2013. "Standard Anatomical and Visual Space for the Mouse Retina: Computational Reconstruction and Transformation of Flattened Retinae with the Retistruct Package," PLOS Computational Biology, Public Library of Science, vol. 9(2), pages 1-10, February.
    4. Rita Gil & Mafalda Valente & Noam Shemesh, 2024. "Rat superior colliculus encodes the transition between static and dynamic vision modes," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:plo:pone00:0111803. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: plosone (email available below). General contact details of provider: https://journals.plos.org/plosone/ .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.