Testing the differential adhesion hypothesis across the epithelial-mesenchymal transition

Steve Pawlizak, Anatol W. Fritsch, Steffen Grosser, Dave Ahrens, Tobias Thalheim, Stefanie Riedel, Tobias R. Kießling, Linda Oswald, Mareike Zink, M. Lisa Manning, Josef A. Käs

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

We analyze the mechanical properties of three epithelial/mesenchymal cell lines (MCF-10A, MDA-MB-231, MDA-MB-436) that exhibit a shift in E-, N- and P-cadherin levels characteristic of an epithelial-mesenchymal transition associated with processes such as metastasis, to quantify the role of cell cohesion in cell sorting and compartmentalization. We develop a unique set of methods to measure cell-cell adhesiveness, cell stiffness and cell shapes, and compare the results to predictions from cell sorting in mixtures of cell populations. We find that the final sorted state is extremely robust among all three cell lines independent of epithelial or mesenchymal state, suggesting that cell sorting may play an important role in organization and boundary formation in tumours. We find that surface densities of adhesive molecules do not correlate with measured cell-cell adhesion, but do correlate with cell shapes, cell stiffness and the rate at which cells sort, in accordance with an extended version of the differential adhesion hypothesis (DAH). Surprisingly, the DAH does not correctly predict the final sorted state. This suggests that these tissues are not behaving as immiscible fluids, and that dynamical effects such as directional motility, friction and jamming may play an important role in tissue compartmentalization across the epithelial-mesenchymal transition.

Original languageEnglish (US)
Article number083049
JournalNew Journal of Physics
Volume17
Issue number8
DOIs
StatePublished - Aug 24 2015

Keywords

  • atomic force microscopy
  • cadherins
  • cell segregation and sorting
  • cellcell adhesion
  • compartmentalization
  • differential adhesion
  • droplet culture

ASJC Scopus subject areas

  • Physics and Astronomy(all)

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  • Cite this

    Pawlizak, S., Fritsch, A. W., Grosser, S., Ahrens, D., Thalheim, T., Riedel, S., Kießling, T. R., Oswald, L., Zink, M., Manning, M. L., & Käs, J. A. (2015). Testing the differential adhesion hypothesis across the epithelial-mesenchymal transition. New Journal of Physics, 17(8), [083049]. https://doi.org/10.1088/1367-2630/17/8/083049