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Cell and Nucleus Shape as an Indicator of Tissue Fluidity in Carcinoma

Steffen Grosser, Jürgen Lippoldt, Linda Oswald, Matthias Merkel, Daniel M. Sussman, Frédéric Renner, Pablo Gottheil, Erik W. Morawetz, Thomas Fuhs, Xiaofan Xie, Steve Pawlizak, Anatol W. Fritsch, Benjamin Wolf, Lars-Christian Horn, Susanne Briest, Bahriye Aktas, M. Lisa Manning, and Josef A. Käs
Phys. Rev. X 11, 011033 – Published 17 February 2021
Physics logo See synopsis: Elongated Cells May Unjam Cancers
An article within the collection: Highlights in Experimental Statistical, Biological, and Soft-Matter Physics
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Abstract

Tissue, cell, and nucleus morphology change during tumor progression. In 2D confluent cell cultures, different tissue states, such as fluid (unjammed) and solid (jammed), are correlated with cell shapes. These results do not have to apply a priori to three dimensions. Cancer cell motility requires and corresponds to a fluidization of the tumor tissue on the bulk level. Here, we investigate bulk tissue fluidity in 3D and determine how it correlates with cell and nucleus shape. In patient samples of mamma and cervix carcinoma, we find areas where cells can move or are immobile. We compare 3D cell spheroids composed of cells from a cancerous and a noncancerous cell line. Through bulk mechanical spheroid-fusion experiments and single live-cell tracking, we show that the cancerous sample is fluidized by active cells moving through the tissue. The healthy, epithelial sample with immobile cells behaves more solidlike. 3D segmentations of the samples show that the degree of tissue fluidity correlates with elongated cell and nucleus shapes. This correlation links cell shapes to cell motility and bulk mechanical behavior. We find two active states of matter in solid tumors: an amorphous glasslike state with characteristics of 3D cell jamming and a disordered fluid state. Individual cell and nucleus shape may serve as a marker for metastatic potential to foster personalized cancer treatment.

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  • Received 28 October 2020
  • Revised 21 December 2020
  • Accepted 23 December 2020

DOI:https://doi.org/10.1103/PhysRevX.11.011033

Published by the American Physical Society under the terms of the Creative Commons Attribution 4.0 International license. Further distribution of this work must maintain attribution to the author(s) and the published article’s title, journal citation, and DOI.

Published by the American Physical Society

Physics Subject Headings (PhySH)

Physics of Living Systems

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This article appears in the following collection:

Highlights in Experimental Statistical, Biological, and Soft-Matter Physics

A collection of recent highlights in experimental Statistical, Biological, and Soft-Matter Physics showcases PRX’s superb quality and topical diversity.

synopsis

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Elongated Cells May Unjam Cancers

Published 17 February 2021

In tightly packed tissues, a cancer cell’s motility is linked to the shape of the cell and of its nucleus.

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Authors & Affiliations

Steffen Grosser1,*, Jürgen Lippoldt1,*, Linda Oswald1,*, Matthias Merkel2, Daniel M. Sussman3, Frédéric Renner1, Pablo Gottheil1, Erik W. Morawetz1, Thomas Fuhs1, Xiaofan Xie1, Steve Pawlizak1, Anatol W. Fritsch1, Benjamin Wolf4, Lars-Christian Horn4, Susanne Briest5, Bahriye Aktas5, M. Lisa Manning3, and Josef A. Käs1,†

  • 1Peter Debye Institute, Leipzig University, Linnéstraße 5, 04103 Leipzig, Germany
  • 2Aix Marseille Univ, Université de Toulon, CNRS, CPT, Turing Center for Living Systems, 13009 Marseille, France
  • 3Department of Physics, Syracuse University, Syracuse, New York 13244, USA
  • 4Institute for Pathology, Leipzig University, 04103 Leipzig, Germany
  • 5Department of Gynecology, Leipzig University, 04103 Leipzig, Germany

  • *These authors contributed equally to this work.
  • jkaes@uni-leipzig.de

Popular Summary

Tumors consist of regions densely packed with cells, which would classically be considered jammed and immotile, and yet cells in these dense tumors do move and divide. To solve this apparent contradiction, researchers have proposed a novel “jamming transition”—where tissues switch between fluid and solid behavior—that allows tissues to fluidize when they are very tightly packed. However, no experimental evidence existed in 3D cancer tissues for jamming and unjamming processes. Using new tracking techniques, we find jammed and unjammed areas in 3D clinical tumor samples.

We systemically study 3D tumor spheroids as a well-controlled model. We find that cell unjamming in 3D tissues correlates with elongated shapes of cells and their nuclei. This observation establishes a link between the physics of cell jamming and classical cancer diagnosis, where shape and appearance of the nucleus are part of the standard evaluation procedure. We find that this new type of shape-induced unjamming occurs at cell elongations that clearly exceed theoretical predictions. Besides jammed and unjammed tissues, we discover that real 3D tissues can switch to a previously unknown intermediate active state to move.

Until now, cell jamming had not been observed in cancerous 3D tissues. Our results support the idea of unjamming as an important step in cancer progression. This fundamentally new concept in the understanding of carcinomas will help to provide more accurate diagnosis.

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Vol. 11, Iss. 1 — January - March 2021

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