Mechanobiological cell adaptations to changing microenvironments determine cancer invasiveness: Experimentally validated finite element modeling.
cancer cell invasion
cell mechanics
finite element modeling
mechanobiology
Journal
Journal of biomedical materials research. Part A
ISSN: 1552-4965
Titre abrégé: J Biomed Mater Res A
Pays: United States
ID NLM: 101234237
Informations de publication
Date de publication:
12 2023
12 2023
Historique:
revised:
30
07
2023
received:
17
04
2023
accepted:
11
08
2023
medline:
3
10
2023
pubmed:
22
8
2023
entrez:
22
8
2023
Statut:
ppublish
Résumé
Metastases are the leading cause of cancer-associated deaths. A key process in metastasis is cell invasiveness, which is driven and controlled by cancer cell interactions with their microenvironment. We have previously shown that invasive cancer cells forcefully push into and indent physiological stiffness gels to cell-scale depths, where the percentage of indenting cells and their attained depths provide clinically relevant predictions of tumor invasiveness and the potential metastatic risk. The cell-attained, invasive indentation depths are directly affected by gel-microenvironment mechanics, which can concurrently modulate the cells' mechanics and force application capacity, in a complex, coordinated mechanobiological response. As it is impossible to experimentally isolate the different contributions of cell and gel mechanics to cancer cell invasiveness, we perform finite element modeling with literature-based parameters. Under average-scale, cell cytoplasm and nucleus mechanics and cell-applied force levels, increasing gel stiffness 1-50 kPa significantly reduced the attained indentation depth by >200%, while the gel's Poisson ratio reduced depths only by up to 20% and only when the ratio was >0.4; this reveals microenvironment mechanics that can promote invasiveness. Experiments with varying-invasiveness cancer cells exhibited qualitative variations in their responses to gel stiffness increase, for example large/small reduction in indentation depth or increase and then reduction. We quantitatively and qualitatively reproduced the different experimental responses via coordinated changes in cell mechanics and applied force levels. Thus, the different cancer cell capacities to adapt their mechanobiology in response to mechanically changing microenvironments likely determine the varying cancer invasiveness and metastatic risk levels in patients.
Substances chimiques
Gels
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1951-1959Informations de copyright
© 2023 The Authors. Journal of Biomedical Materials Research Part A published by Wiley Periodicals LLC.
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