title: The effect of Young's modulus on the neuronal differentiation of mouse embryonic stem cells.
abstract: 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 2 kPa to 18 kPa to finally 35 kPa. Attachment was found to decrease with increasing stiffness for both ESC's (with a 95% decrease on 35 kPa compared to 2 kPa) and neural precursors (with a 83% decrease on 35 kPa). 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. 2 kPa 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.
authors.affiliation: Advanced Centre for Biochemical Engineering, University College London, Torrington Place, London WC1E 7JE, United Kingdom.
authors.forename: Shahzad
authors.initials: S
authors.lastname: Ali
authors.affiliation: Advanced Centre for Biochemical Engineering, University College London, Torrington Place, London WC1E 7JE, United Kingdom.
authors.forename: Ivan B
authors.initials: IB
authors.lastname: Wall
authors.affiliation: Advanced Centre for Biochemical Engineering, University College London, Torrington Place, London WC1E 7JE, United Kingdom.
authors.forename: Chris
authors.initials: C
authors.lastname: Mason
authors.affiliation: The Pelling Lab, University of Ottawa, Center for Interdisciplinary Nanophysics, MacDonald Hall (MCD), 150 Louis Pasteur, Ottawa, ON K1N6N5, Canada.
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Pelling
authors.affiliation: Advanced Centre for Biochemical Engineering, University College London, Torrington Place, London WC1E 7JE, United Kingdom. Electronic address: f.veraitch@ucl.ac.uk.
authors.forename: Farlan S
authors.initials: FS
authors.lastname: Veraitch
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D055119:Elastic Modulus / Q000187:drug effects; D005780:Gelatin / Q000737:chemistry; D005976:Glutaral / Q000737:chemistry; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D015739:Nocodazole / Q000494:pharmacology; D010641:Phenotype; D014404:Tubulin / Q000378:metabolism
chemical_list: D015415:Biomarkers; D006576:Heterocyclic Compounds, 4 or More Rings; D008869:Microtubule-Associated Proteins; C079240:Mtap2 protein, mouse; D014404:Tubulin; C472645:blebbistatin; D005780:Gelatin; D015739:Nocodazole; D005976:Glutaral
keywords: Atomic force microscopy; Embryonic stem cells; Neuronal differentiation; Young’s modulus