title: The control of chromosome segregation during mitosis in epithelial cells by substrate elasticity.
abstract: Materials of defined elasticity, including synthetic material scaffolds and tissue-derived matrices, can regulate biological responses of cells and in particular adhesion, migration, growth and differentiation which are essential parameters for tissue integration. These responses have been extensively investigated in interphase cells, but little is known whether and how material elasticity affects mitotic cells. We used polyelectrolyte multilayer films as model substrates with elastic modulus ranging from Eap = 0 up to Eap = 500 kPa and mitotic PtK2 epithelial cells to address these important questions. Soft substrates (Eap < 50 kPa) led to abnormal morphology in chromosome segregation, materialized by chromatin bridges and chromosome lagging. Frequency of these damages increased with decreasing substrate stiffness and was correlated with a pro-apoptotic phenotype. Mitotic spindle was not observed on soft substrates where formation of chromatin damages is due to low β1-integrin engagement and decrease of Rac1 activities. This work constitutes the first evidence that soft substrates hinder epithelial cell division. In perspective, our findings emphasize the prime incidence of the material elasticity on the fate of the phenotype, especially of stem cells in the mitotic phase.
authors: Institut National de la Santé et de la Recherche Médicale, INSERM Unité 977, 11 rue Humann, 67085 Strasbourg Cedex, France.
authors: Leyla
authors: L
authors: Kocgozlu
authors: Morgane
authors: M
authors: Rabineau
authors: Géraldine
authors: G
authors: Koenig
authors: Youssef
authors: Y
authors: Haikel
authors: Pierre
authors: P
authors: Schaaf
authors: Jean-Noel
authors: JN
authors: Freund
authors: Jean-Claude
authors: JC
authors: Voegel
authors: Philippe
authors: P
authors: Lavalle
authors: Dominique
authors: D
authors: Vautier
mesh_terms: D000818:Animals; D017209:Apoptosis; D001672:Biocompatible Materials / Q000378:metabolism; D015153:Blotting, Western; D002460:Cell Line; D020090:Chromosome Segregation / Q000235:genetics / Q000502:physiology*; D055119:Elastic Modulus / Q000502:physiology; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism*; D008938:Mitosis / Q000235:genetics / Q000502:physiology*; D051381:Rats; D008941:Spindle Apparatus / Q000378:metabolism
chemical_list: D001672:Biocompatible Materials