Cell guidance into quiescent state through chromatin remodeling induced by elastic modulus of substrate.
Substrate stiffness is known to strongly influence the fate of adhering cells. Yet, little is known about the influence of the substrate stiffness on chromatin. Chromatin integrates a multitude of biochemical signals interpreted by activation or gene silencing. Here we investigate for the first time the organization of chromatin of epithelial cells on substrate with various mechanical properties. On stiff substrates (100-200 kPa), where cells preferentially adhere, chromatin is mainly found in its euchromatin form. Decreasing the Young modulus to 50 kPa is correlated with a partial shift from euchromatin to heterochromatin. On very soft substrates (≪10 kPa) this is accompanied by cell lysis. On these very soft substrates, histone deacetylase inhibition by adding a drug preserves acetylated histone and thus maintains the euchromatin form, thereby keeping intact the nuclear envelope as well as a residual intermediate filament network around the nucleus. This allows cells to survive in a non-adherent state without undergoing proliferation. When transfer on a stiff substrate these cells retain their capacity to adhere, to spread and to enter a novel mitotic cycle. A similar effect is observed on soft substrates (50 kPa) without need of histone deacetylase inhibition. These new results suggest that on soft substrates cells might enter in a quiescence state. Cell quiescence may thus be triggered by the Young modulus of a substrate, a major result for strategies focusing on the design of scaffold in tissue engineering.
['Rabineau|Morgane|M|', 'Flick|Florence|F|', 'Mathieu|Eric|E|', 'Tu|Annie|A|', 'Senger|Bernard|B|', 'Voegel|Jean-Claude|JC|', 'Lavalle|Philippe|P|', 'Schaaf|Pierre|P|', 'Freund|Jean-Noël|JN|', 'Haikel|Youssef|Y|', 'Vautier|Dominique|D|']
D000818:Animals D016923:Cell Death D002460:Cell Line D002470:Cell Survival D042002:Chromatin Assembly and Disassembly D000090266:Chromobox Protein Homolog 5 D002868:Chromosomal Proteins, Non-Histone D003599:Cytoskeleton D055119:Elastic Modulus D004573:Electrolytes D004847:Epithelial Cells D022041:Euchromatin D006570:Heterochromatin D000076245:Heterogeneous Nuclear Ribonucleoprotein A1 D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B D056572:Histone Deacetylase Inhibitors D006655:Histone Deacetylases D006877:Hydroxamic Acids D013379:Substrate Specificity D014158:Transcription, Genetic
Substrate stiffness Histone deacetylase inhibition Nucleus Biomaterials Chromatin plasticity Polyelectrolyte multilayer films