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Biol Open. 2019 Jan 24;8(1). pii: bio037051. doi: 10.1242/bio.037051.

E-cadherin, actin, microtubules and FAK dominate different spheroid formation phases and important elements of tissue integrity.

Author information

1
Physical Biology/Physikalische Biologie (IZN, FB 15), Buchmann Institute for Molecular Life Sciences (BMLS), Cluster of Excellence Frankfurt - Macromolecular Complexes (CEF - MC), Goethe Universität - Frankfurt am Main (Campus Riedberg), Max-von-Laue-Straße 15, D-60348 Frankfurt am Main, Germany.
2
Physical Biology/Physikalische Biologie (IZN, FB 15), Buchmann Institute for Molecular Life Sciences (BMLS), Cluster of Excellence Frankfurt - Macromolecular Complexes (CEF - MC), Goethe Universität - Frankfurt am Main (Campus Riedberg), Max-von-Laue-Straße 15, D-60348 Frankfurt am Main, Germany ernst.stelzer@physikalischebiologie.de.

Abstract

Spheroids resemble features of tissues and serve as model systems to study cell-cell and cell-ECM interactions in non-adhesive three-dimensional environments. Although it is generally accepted that mature spheroids resemble tissue properties very well, no studies relate different phases in the spheroid formation processes that contribute to tissue integrity. Tissue integrity involves the cellular processes adhesion formation, adhesion reinforcement, rearrangement as well as proliferation. They maintain the structure and function of tissues and, upon dysregulation, contribute to malignancy. We investigated spheroid formation dynamics in cell lines of different metastatic potential. We dissected spheroid formation into phases of aggregation, compaction and growth to identify the respective contributions of E-cadherin, actin, microtubules and FAK. E-cadherin, actin and microtubules drive the first two phases. Microtubules and FAK are involved in the proliferation phase. FAK activity correlates with the metastatic potential of the cells. A robust computational model based on a very large number of experiments reveals the temporal resolution of cell adhesion. Our results provide novel hypotheses to unveil the general mechanisms that contribute to tissue integrity.

KEYWORDS:

Adhesion; Spheroids; Three-dimensional cell culture; Tissue integrity

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