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Biomechanics and Modeling in Mechanobiology

, Volume 13, Issue 2, pp 417–435 | Cite as

Cellular contractility and substrate elasticity: a numerical investigation of the actin cytoskeleton and cell adhesion

  • William Ronan
  • Vikram S. Deshpande
  • Robert M. McMeeking
  • J. Patrick McGarry
Original Paper

Abstract

Numerous experimental studies have established that cells can sense the stiffness of underlying substrates and have quantified the effect of substrate stiffness on stress fibre formation, focal adhesion area, cell traction, and cell shape. In order to capture such behaviour, the current study couples a mixed mode thermodynamic and mechanical framework that predicts focal adhesion formation and growth with a material model that predicts stress fibre formation, contractility, and dissociation in a fully 3D implementation. Simulations reveal that SF contractility plays a critical role in the substrate-dependent response of cells. Compliant substrates do not provide sufficient tension for stress fibre persistence, causing dissociation of stress fibres and lower focal adhesion formation. In contrast, cells on stiffer substrates are predicted to contain large amounts of dominant stress fibres. Different levels of cellular contractility representative of different cell phenotypes are found to alter the range of substrate stiffness that cause the most significant changes in stress fibre and focal adhesion formation. Furthermore, stress fibre and focal adhesion formation evolve as a cell spreads on a substrate and leading to the formation of bands of fibres leading from the cell periphery over the nucleus. Inhibiting the formation of FAs during cell spreading is found to limit stress fibre formation. The predictions of this mutually dependent material-interface framework are strongly supported by experimental observations of cells adhered to elastic substrates and offer insight into the inter-dependent biomechanical processes regulating stress fibre and focal adhesion formation.

Keywords

Stress fibre contractility Focal adhesion formation  Substrate elasticity Nucleus stress  Finite element  Active constitutive formulation 

Notes

Acknowledgments

Funding support was provided by the Irish Research Council for Science, Engineering and Technology (IRCSET) postgraduate scholarship under the EMBARK initiative and by the Science Foundation Ireland Research Frontiers Programme (SFI-RFP/ENM1726). The authors acknowledge the SFI/ HEA Irish Centre for High-End Computing (ICHEC) for the provision of computational facilities and support.

Supplementary material

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Supplementary material 1 (tif 880 KB)
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Supplementary material 2 (tif 1727 KB)
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Supplementary material 3 (mp4 962 KB)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • William Ronan
    • 1
  • Vikram S. Deshpande
    • 2
  • Robert M. McMeeking
    • 3
    • 4
  • J. Patrick McGarry
    • 1
  1. 1.Department of Mechanical and Biomedical Engineering National University of Ireland Galway GalwayIreland
  2. 2.Department of EngineeringUniversity of CambridgeCambridgeUK
  3. 3.Departments of Mechanical Engineering MaterialsUniversity of CaliforniaSanta BarbaraUSA
  4. 4.School of EngineeringUniversity of Aberdeen King’s CollegeAberdeenScotland, UK

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