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, Mary Elizabeth Manning, Josef A. Käs

Research output: Contribution to journalArticle

26 Citations (Scopus)

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

Fingerprint

adhesion
cells
classifying
multiple docking adapters
cultured cells
stiffness
jamming
locomotion
cohesion
metastasis
adhesives
friction
tumors
mechanical properties
fluids
shift
predictions
molecules

Keywords

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

ASJC Scopus subject areas

  • Physics and Astronomy(all)

Cite this

Pawlizak, S., Fritsch, A. W., Grosser, S., Ahrens, D., Thalheim, T., Riedel, S., ... 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

Testing the differential adhesion hypothesis across the epithelial-mesenchymal transition. / Pawlizak, Steve; Fritsch, Anatol W.; Grosser, Steffen; Ahrens, Dave; Thalheim, Tobias; Riedel, Stefanie; Kießling, Tobias R.; Oswald, Linda; Zink, Mareike; Manning, Mary Elizabeth; Käs, Josef A.

In: New Journal of Physics, Vol. 17, No. 8, 083049, 24.08.2015.

Research output: Contribution to journalArticle

Pawlizak, S, Fritsch, AW, Grosser, S, Ahrens, D, Thalheim, T, Riedel, S, Kießling, TR, Oswald, L, Zink, M, Manning, ME & Käs, JA 2015, 'Testing the differential adhesion hypothesis across the epithelial-mesenchymal transition', New Journal of Physics, vol. 17, no. 8, 083049. https://doi.org/10.1088/1367-2630/17/8/083049
Pawlizak S, Fritsch AW, Grosser S, Ahrens D, Thalheim T, Riedel S et al. Testing the differential adhesion hypothesis across the epithelial-mesenchymal transition. New Journal of Physics. 2015 Aug 24;17(8). 083049. https://doi.org/10.1088/1367-2630/17/8/083049
Pawlizak, Steve ; Fritsch, Anatol W. ; Grosser, Steffen ; Ahrens, Dave ; Thalheim, Tobias ; Riedel, Stefanie ; Kießling, Tobias R. ; Oswald, Linda ; Zink, Mareike ; Manning, Mary Elizabeth ; Käs, Josef A. / Testing the differential adhesion hypothesis across the epithelial-mesenchymal transition. In: New Journal of Physics. 2015 ; Vol. 17, No. 8.
@article{022defaaa7ba4c75a0d0009fc4bcc404,
title = "Testing the differential adhesion hypothesis across the epithelial-mesenchymal transition",
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.",
keywords = "atomic force microscopy, cadherins, cell segregation and sorting, cellcell adhesion, compartmentalization, differential adhesion, droplet culture",
author = "Steve Pawlizak and Fritsch, {Anatol W.} and Steffen Grosser and Dave Ahrens and Tobias Thalheim and Stefanie Riedel and Kie{\ss}ling, {Tobias R.} and Linda Oswald and Mareike Zink and Manning, {Mary Elizabeth} and K{\"a}s, {Josef A.}",
year = "2015",
month = "8",
day = "24",
doi = "10.1088/1367-2630/17/8/083049",
language = "English (US)",
volume = "17",
journal = "New Journal of Physics",
issn = "1367-2630",
publisher = "IOP Publishing Ltd.",
number = "8",

}

TY - JOUR

T1 - Testing the differential adhesion hypothesis across the epithelial-mesenchymal transition

AU - Pawlizak, Steve

AU - Fritsch, Anatol W.

AU - Grosser, Steffen

AU - Ahrens, Dave

AU - Thalheim, Tobias

AU - Riedel, Stefanie

AU - Kießling, Tobias R.

AU - Oswald, Linda

AU - Zink, Mareike

AU - Manning, Mary Elizabeth

AU - Käs, Josef A.

PY - 2015/8/24

Y1 - 2015/8/24

N2 - 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.

AB - 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.

KW - atomic force microscopy

KW - cadherins

KW - cell segregation and sorting

KW - cellcell adhesion

KW - compartmentalization

KW - differential adhesion

KW - droplet culture

UR - http://www.scopus.com/inward/record.url?scp=84941686554&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84941686554&partnerID=8YFLogxK

U2 - 10.1088/1367-2630/17/8/083049

DO - 10.1088/1367-2630/17/8/083049

M3 - Article

AN - SCOPUS:84941686554

VL - 17

JO - New Journal of Physics

JF - New Journal of Physics

SN - 1367-2630

IS - 8

M1 - 083049

ER -