The effect of Young’s modulus on the neuronal differentiation of mouse embryonic stem cells

• Published in: Acta biomaterialia 2015-10, Vol.25, p.253-267
• Main Authors: Ali, Shahzad, Wall, Ivan B., Mason, Chris, Pelling, Andrew E., Veraitch, Farlan S.
• Format: Article
• Language: English
• Subjects: Animals; Atomic force microscopy; Attachment; Biomarkers - metabolism; Cell Adhesion - drug effects; Cell Differentiation - drug effects; Differentiation; Elastic Modulus - drug effects; Electrochemical machining; Embryonic stem cells; Gelatin - chemistry; Glutaral - chemistry; Heterocyclic Compounds, 4 or More Rings - pharmacology; Mice; Microtubule-Associated Proteins - metabolism; Microtubules - drug effects; Microtubules - metabolism; Modulus of elasticity; Mouse Embryonic Stem Cells - cytology; Mouse Embryonic Stem Cells - drug effects; Mouse Embryonic Stem Cells - metabolism; Neuronal differentiation; Neurons; Neurons - cytology; Neurons - drug effects; Neurons - metabolism; Nocodazole - pharmacology; Phenotype; Precursors; Stem cells; Stiffness; Tubulin - metabolism; Young’s modulus
• ISSN: 1742-7061; 1878-7568
• DOI: 10.1016/j.actbio.2015.07.008

[Display omitted] There is substantial evidence that cells produce a diverse response to changes in ECM stiffness depending on their identity. Our aim was to understand how stiffness impacts neuronal differentiation of embryonic stem cells (ESC’s), and how this varies at three specific stages of the differentiation process. In this investigation, three effects of stiffness on cells were considered; attachment, expansion and phenotypic changes during differentiation. Stiffness was varied from 2kPa to 18kPa to finally 35kPa. Attachment was found to decrease with increasing stiffness for both ESC’s (with a 95% decrease on 35kPa compared to 2kPa) and neural precursors (with a 83% decrease on 35kPa). The attachment of immature neurons was unaffected by stiffness. Expansion was independent of stiffness for all cell types, implying that the proliferation of cells during this differentiation process was independent of Young’s modulus. Stiffness had no effect upon phenotypic changes during differentiation for mESC’s and neural precursors. 2kPa increased the proportion of cells that differentiated from immature into mature neurons. Taken together our findings imply that the impact of Young’s modulus on attachment diminishes as neuronal cells become more mature. Conversely, the impact of Young’s modulus on changes in phenotype increased as cells became more mature.