13th Annual Symposium
Physics of Cancer
Leipzig, Germany
Sept 28 - 30, 2022
Poster
Yield stress: A tipping point of cell unjamming.
Xiaofan Xie, Steffen Grosser, Jürgen Lippoldt, Carlotta Ficorella, Thomas Fuhs, Josef Käs
Peter Debye Institute for Soft Matter Physics, University of Leipzig, Linnéstraße 5, Leipzig, Germany
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Cell unjamming as a collective cell behavior, has been showing its nonnegligible impact on tissue mechanics. Jammed cells are caged in their position by surrounding cells or extracellular matrix (ECM) in healthy tissue to form a solid-like state cell clusters, whereas unjammed cells tend to behave more motile than jammed cells and forming a fluid-like state cell clusters in tumor[1]. Previous studies have shown that in the histological images of tumors, solid regions of jammed stiff cancer cells are embedded in a fluid sea of soft motile cancer cells[2]. We also noted that the mechanical behavior differed in the core/shell region even in a simple system of cell clusters. As we further manipulated the mechanics of cell cytoskeletons with Cytochalasin D and (−)-Blebbistatin, and combing the metastatic cell behavior of the same cell types under the constriction[3], we firmly believe that cell nuclei have mastered their cytoskeletal properties and dominate the whole tissue mechanics for cancerous mesenchymal cells. Therefore, the study of the mechanics of nuclei and its connection to cell unjamming behavior becomes highly critical to investigate the metastatic potential of cancer cells.
Here, we present a novel approach to measuring the yield stress a cell must overcome to become motile (unjammed) in tissues. By specifically probing the nucleus region of cells under the Atomic Force Microscope (AFM) and combining the morphological change of the cell nucleus during cell unjamming transition, we are able to establish a connection between the cell nucleus-based yield stress to its motility. To serve a larger picture, deriving an unjamming-based marker that detects the ability of cells to move in the static histological images, which will be a landmark to understand the role of the cancer cell unjamming in the metastatic cascade.
[1]Fuhs, T., et al.Rigid tumors contain soft cancer cells, Nature Physics (manuscript accepted) (2022)
[2]Grosser, S., et al.Cell and nucleus shape as an indicator of tissue fluidity in carcinoma., Physical Review X 11(1): 011033 (2021)
[3]Ficorella, C., et al.Intermediate filaments ensure resiliency of single carcinoma cells, while active contractility of the actin cortex determines their invasive potential., New Journal of Physics 23(8): 083028 (2021)
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