The control of chromosome segregation during mitosis in epithelial cells by substrate elasticity.
Biomaterials
; 33(3): 798-809, 2012 Jan.
Article
em En
| MEDLINE
| ID: mdl-22041225
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 ß1-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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Segregação de Cromossomos
/
Células Epiteliais
/
Mitose
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Biomaterials
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
França