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...

全面介绍

书目详细资料
Main Authors: Roberts, Anya B, Zhang, Jitao, Raj Singh, Vijay, Nikolić, Miloš, Moeendarbary, Emad, Kamm, Roger D, So, Peter TC, Scarcelli, Giuliano
其他作者: Massachusetts Institute of Technology. Department of Biological Engineering
格式: 文件
语言:English
出版: Elsevier BV 2022
在线阅读:https://hdl.handle.net/1721.1/143442
实物特征
总结: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.