Intravital measurements of solid stresses in tumours reveal length-scale and microenvironmentally dependent force transmission.
Journal
Nature biomedical engineering
ISSN: 2157-846X
Titre abrégé: Nat Biomed Eng
Pays: England
ID NLM: 101696896
Informations de publication
Date de publication:
Nov 2023
Nov 2023
Historique:
received:
27
05
2022
accepted:
19
07
2023
medline:
17
11
2023
pubmed:
29
8
2023
entrez:
28
8
2023
Statut:
ppublish
Résumé
In cancer, solid stresses impede the delivery of therapeutics to tumours and the trafficking and tumour infiltration of immune cells. Understanding such consequences and the origin of solid stresses requires their probing in vivo at the cellular scale. Here we report a method for performing volumetric and longitudinal measurements of solid stresses in vivo, and findings from its applicability to tumours. We used multimodal intravital microscopy of fluorescently labelled polyacrylamide beads injected in breast tumours in mice as well as mathematical modelling to compare solid stresses at the single-cell and tissue scales, in primary and metastatic tumours, in vitro and in mice, and in live mice and post-mortem tissue. We found that solid-stress transmission is scale dependent, with tumour cells experiencing lower stresses than their embedding tissue, and that tumour cells in lung metastases experience substantially higher solid stresses than those in the primary tumours. The dependence of solid stresses on length scale and the microenvironment may inform the development of therapeutics that sensitize cancer cells to such mechanical forces.
Identifiants
pubmed: 37640900
doi: 10.1038/s41551-023-01080-8
pii: 10.1038/s41551-023-01080-8
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1473-1492Subventions
Organisme : U.S. Department of Health and Human Services | NIH | NIH Office of the Director (OD)
ID : S10OD024993
Organisme : U.S. Department of Health and Human Services | National Institutes of Health (NIH)
ID : DP2HL168562
Organisme : U.S. Department of Health and Human Services | National Institutes of Health (NIH)
ID : R21EB031332
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Nature Limited.
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