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The control of chromosome segregation during mitosis in epithelial cells by substrate elasticity

Paper ID Volume ID Publish Year Pages File Format Full-Text
7045 530 2012 12 PDF Available
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.

Keywords
Polyelectrolyte multilayer films; Biomaterials; Substrate elasticity; Integrin; Chromosome missegregation; Apoptosis
First Page Preview
The control of chromosome segregation during mitosis in epithelial cells by substrate elasticity
Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 33, Issue 3, January 2012, Pages 798–809
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering