Tumor cell nuclei soften during transendothelial migration

Anya B Roberts; Jitao Zhang; Vijay Raj Singh; Miloš Nikolić; Emad Moeendarbary; Roger D Kamm; Peter T C So; Giuliano Scarcelli

doi:10.1016/j.jbiomech.2021.110400

Tumor cell nuclei soften during transendothelial migration

J Biomech. 2021 May 24:121:110400. doi: 10.1016/j.jbiomech.2021.110400. Epub 2021 Apr 5.

Authors

Anya B Roberts¹, Jitao Zhang², Vijay Raj Singh³, Miloš Nikolić⁴, Emad Moeendarbary⁵, Roger D Kamm⁶, Peter T C So⁷, Giuliano Scarcelli⁸

Affiliations

¹ Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge 02139, MA, USA.
² Fischell Department of Bioengineering, University of Maryland, College Park 20742, MD, USA.
³ Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge 02139, MA, USA; Laser Biomedical Research Center, Massachusetts Institute of Technology, Cambridge 02139, MA, USA.
⁴ Maryland Biophysics Program, University of Maryland, College Park, MD 20742, USA.
⁵ Department of Mechanical Engineering, University College London, London WC1E 7JE, UK.
⁶ Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge 02139, MA, USA; Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge 02139, MA, USA. Electronic address: rdkamm@mit.edu.
⁷ Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge 02139, MA, USA; Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge 02139, MA, USA; Laser Biomedical Research Center, Massachusetts Institute of Technology, Cambridge 02139, MA, USA. Electronic address: ptso@mit.edu.
⁸ Fischell Department of Bioengineering, University of Maryland, College Park 20742, MD, USA; Maryland Biophysics Program, University of Maryland, College Park, MD 20742, USA. Electronic address: sarc@umd.edu.

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.

Keywords: Brillouin microscopy; Cell modulus; Interference microscopy; Metastasis.

Publication types

Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Cell Line, Tumor
Cell Movement
Cell Nucleus
Collagen
Humans
Microscopy, Confocal
Neoplasms*
Transendothelial and Transepithelial Migration*

Substances

Collagen

Abstract

Publication types

MeSH terms

Substances

Grants and funding