Tumor cell nuclei soften during transendothelial migration

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 distrib...

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Main Authors: Roberts, Anya B, Zhang, Jitao, Raj Singh, Vijay, Nikolić, Miloš, Moeendarbary, Emad, Kamm, Roger D, So, Peter TC, Scarcelli, Giuliano
Other Authors: Massachusetts Institute of Technology. Department of Biological Engineering
Format: Article
Language:English
Published: Elsevier BV 2022
Online Access:https://hdl.handle.net/1721.1/143442
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author Roberts, Anya B
Zhang, Jitao
Raj Singh, Vijay
Nikolić, Miloš
Moeendarbary, Emad
Kamm, Roger D
So, Peter TC
Scarcelli, Giuliano
author2 Massachusetts Institute of Technology. Department of Biological Engineering
author_facet Massachusetts Institute of Technology. Department of Biological Engineering
Roberts, Anya B
Zhang, Jitao
Raj Singh, Vijay
Nikolić, Miloš
Moeendarbary, Emad
Kamm, Roger D
So, Peter TC
Scarcelli, Giuliano
author_sort Roberts, Anya B
collection MIT
description 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.
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spelling mit-1721.1/1434422023-02-13T18:35:47Z Tumor cell nuclei soften during transendothelial migration Roberts, Anya B Zhang, Jitao Raj Singh, Vijay Nikolić, Miloš Moeendarbary, Emad Kamm, Roger D So, Peter TC Scarcelli, Giuliano Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Mechanical Engineering Massachusetts Institute of Technology. Laser Biomedical Research Center 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. 2022-06-15T16:48:18Z 2022-06-15T16:48:18Z 2021 2022-06-15T16:45:21Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/143442 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. en 10.1016/J.JBIOMECH.2021.110400 Journal of Biomechanics Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier BV PMC
spellingShingle Roberts, Anya B
Zhang, Jitao
Raj Singh, Vijay
Nikolić, Miloš
Moeendarbary, Emad
Kamm, Roger D
So, Peter TC
Scarcelli, Giuliano
Tumor cell nuclei soften during transendothelial migration
title Tumor cell nuclei soften during transendothelial migration
title_full Tumor cell nuclei soften during transendothelial migration
title_fullStr Tumor cell nuclei soften during transendothelial migration
title_full_unstemmed Tumor cell nuclei soften during transendothelial migration
title_short Tumor cell nuclei soften during transendothelial migration
title_sort tumor cell nuclei soften during transendothelial migration
url https://hdl.handle.net/1721.1/143442
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