Tumor cell nuclei soften during transendothelial migration
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nihms-1716658.pdf
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Accepted version
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Author(s) • • • • • • •
Roberts, Anya B
Zhang, Jitao
Raj Singh, Vijay
Nikolić, Miloš
Moeendarbary, Emad
Kamm, Roger D
So, Peter TC
Scarcelli, Giuliano
Date Issued
2021
Journal
Journal of Biomechanics
Publisher
Elsevier BV
Citation
Roberts, Anya B, Zhang, Jitao, Raj Singh, Vijay, Nikolić, Miloš, Moeendarbary, Emad et al. 2021. "Tumor cell nuclei soften during transendothelial migration." Journal of Biomechanics, 121.
Version
Author's final manuscript
Abstract
During cancer metastasis, tumor cells undergo significant deformation in order to traverse through endothelial cell junctions in the walls of blood vessels. As cells pass through narrow gaps, smaller than the nuclear diameter, the spatial configuration of chromatin must change along with the distribution of nuclear enzymes. Nuclear stiffness is an important determinant of the ability of cells to undergo transendothelial migration, yet no studies have been conducted to assess whether tumor cell cytoskeletal or nuclear stiffness changes during this critical process in order to facilitate passage. To address this question, we employed two non-contact methods, Brillouin confocal microscopy (BCM) and confocal reflectance quantitative phase microscopy (QPM), to track the changes in mechanical properties of live, transmigrating tumor cells in an in vitro collagen gel platform. Using these two imaging modalities to study transmigrating MDA-MB-231, A549, and A375 cells, we found that both the cells and their nuclei soften upon extravasation and that the nuclear membranes remain soft for at least 24 h. These new data suggest that tumor cells adjust their mechanical properties in order to facilitate extravasation.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Mechanical Engineering
Massachusetts Institute of Technology. Laser Biomedical Research Center
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DOI of Published Version
https://doi.org/10.1016/J.JBIOMECH.2021.110400