Tumor cell nuclei soften during transendothelial migration

JOURNAL OF BIOMECHANICS

卷:121

Article

Roberts, Anya B.¹  Zhang, Jitao²  Singh, Vijay Raj^3,4  Nikolic, Milos⁵  Moeendarbary, Emad⁶  Kamm, Roger D.^1,3  So, Peter T. C.^1,3,4  Scarcelli, Giuliano^2,5 

[1] MIT, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA

[2] Univ Maryland, Fischell Dept Bioengn, College Pk, MD 20742 USA

[3] MIT, Dept Mech Engn, Cambridge, MA 02139 USA

[4] MIT, Laser Biomed Res Ctr, Cambridge, MA 02139 USA

[5] Univ Maryland, Maryland Biophys Program, College Pk, MD 20742 USA

[6] UCL, Dept Mech Engn, London WC1E 7JE, England

关键词: Brillouin microscopy;    Interference microscopy;    Metastasis;    Cell modulus;   

DOI  :  10.1016/j.jbiomech.2021.110400

来源: Elsevier

【 摘 要 】

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. (c) 2021 Elsevier Ltd. All rights reserved.

【 授权许可】

Free