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What are the key mechanical mechanisms governing integrin-mediated cell migration in three-dimensional fiber networks?
Citation Link: https://doi.org/10.15480/882.8022
Publikationstyp
Journal Article
Publikationsdatum
2023
Sprache
English
Enthalten in
Volume
22
Start Page
1177
End Page
1192
Citation
Biomechanics and Modeling in Mechanobiology (22): 1177-1192 (2023)
Publisher DOI
Scopus ID
Publisher
Springer
Cell migration plays a vital role in numerous processes such as development, wound healing, or cancer. It is well known that numerous complex mechanisms are involved in cell migration. However, so far it remains poorly understood what are the key mechanisms required to produce the main characteristics of this behavior. The reason is a methodological one. In experimental studies, specific factors and mechanisms can be promoted or inhibited. However, while doing so, there can always be others in the background which play key roles but which have simply remained unattended so far. This makes it very difficult to validate any hypothesis about a minimal set of factors and mechanisms required to produce cell migration. To overcome this natural limitation of experimental studies, we developed a computational model where cells and extracellular matrix fibers are represented by discrete mechanical objects on the micrometer scale. In this model, we had exact control of the mechanisms by which cells and matrix fibers interacted with each other. This enabled us to identify the key mechanisms required to produce physiologically realistic cell migration (including advanced phenomena such as durotaxis and a biphasic relation between migration efficiency and matrix stiffness). We found that two main mechanisms are required to this end: a catch-slip bond of individual integrins and cytoskeletal actin-myosin contraction. Notably, more advanced phenomena such as cell polarization or details of mechanosensing were not necessary to qualitatively reproduce the main characteristics of cell migration observed in experiments.
Schlagworte
Cell migration
Computational modeling
Durotaxis
Fibrous networks
Tissue engineering
DDC Class
500: Science
Publication version
publishedVersion
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s10237-023-01709-2.pdf
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