Modeling the extracellular matrix in cell migration and morphogenesis: a guide for the curious biologist

Rebecca M. Crossley, Samuel Johnson, Erika Tsingos, Zoe Bell, Massimiliano Berardi, Margherita Botticelli, Quirine J. S. Braat, John Metzcar, Marco Ruscone, Yuan Yin, Robyn Shuttleworth*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

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Abstract

The extracellular matrix (ECM) is a highly complex structure through which biochemical and mechanical signals are transmitted. In processes of cell migration, the ECM also acts as a scaffold, providing structural support to cells as well as points of potential attachment. Although the ECM is a well-studied structure, its role in many biological processes remains difficult to investigate comprehensively due to its complexity and structural variation within an organism. In tandem with experiments, mathematical models are helpful in refining and testing hypotheses, generating predictions, and exploring conditions outside the scope of experiments. Such models can be combined and calibrated with in vivo and in vitro data to identify critical cell-ECM interactions that drive developmental and homeostatic processes, or the progression of diseases. In this review, we focus on mathematical and computational models of the ECM in processes such as cell migration including cancer metastasis, and in tissue structure and morphogenesis. By highlighting the predictive power of these models, we aim to help bridge the gap between experimental and computational approaches to studying the ECM and to provide guidance on selecting an appropriate model framework to complement corresponding experimental studies.
Original languageEnglish
Article number1354132
JournalFrontiers in cell and developmental biology
Volume12
DOIs
Publication statusPublished - 1 Mar 2024

Bibliographical note

Funding:
The author(s) declare financial support was received for the research, authorship, and/or publication of this article. RMC is supported by funding from the Engineering and Physical Sciences Research Council (EP/T517811/1) and the Oxford-Wolfson-Marriott scholarship at Wolfson College, University of Oxford. SJ receives funding from the Biotechnology and Biological Sciences Research Council (BBSRC) (BB/T008784/1). ET is funded by the Dutch Research Council (NWO) grant number VI. Veni.222.323. ZB is supported by funding from the Engineering and Physical Sciences Research Council (EP/T517914/1). QJSB is funded by Dutch Research Council (NWO) by the ENW-XL program ‘Active Matter Physics of Collective Metastasis’ (OCENW.GROOT.2019.022). JM was supported in part by NSF Grant 1735095 - NRT: Interdisciplinary Training in Complex Networks and Systems, the Jayne Koskinas Ted Giovanis Foundation for Health and Policy, and the Breast Cancer Research Foundation. MR is funded by PerMedCoE (H2020-ICT-951773). YY is funded by the Engineering and Physical Sciences Research Council (EP/W524311/1) and supported by the Travel for Research and Study Grant at St Hilda’s College, University of Oxford.

Keywords

  • cancer
  • ECM structure
  • mathematical modeling
  • wound healing
  • extracellular matrix
  • tissue morphogenesis

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