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Tumor cell nuclei soften during transendothelial migration

Roberts, AB; Zhang, J; Raj Singh, V; Nikolić, M; Moeendarbary, E; Kamm, RD; So, PTC; (2021) Tumor cell nuclei soften during transendothelial migration. Journal of Biomechanics , 121 , Article 110400. 10.1016/j.jbiomech.2021.110400. Green open access

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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.

Type: Article
Title: Tumor cell nuclei soften during transendothelial migration
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.jbiomech.2021.110400
Publisher version: https://doi.org/10.1016/j.jbiomech.2021.110400
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Brillouin microscopy, Cell modulus, Interference microscopy, Metastasis
UCL classification: UCL
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Mechanical Engineering
URI: https://discovery.ucl.ac.uk/id/eprint/10126915
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