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Publication : Intravital measurements of solid stresses in tumours reveal length-scale and microenvironmentally dependent force transmission.

First Author  Zhang S Year  2023
Journal  Nat Biomed Eng Volume  7
Issue  11 Pages  1473-1492
PubMed ID  37640900 Mgi Jnum  J:380170
Mgi Id  MGI:8279148 Doi  10.1038/s41551-023-01080-8
Citation  Zhang S, et al. (2023) Intravital measurements of solid stresses in tumours reveal length-scale and microenvironmentally dependent force transmission. Nat Biomed Eng 7(11):1473-1492
abstractText  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.
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