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*

*Corresponding author for this work

Research output: Contribution to journalArticle

25 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)417-435
Number of pages19
JournalBiomechanics and Modeling in Mechanobiology
Volume13
Issue number2
Early online date18 Jun 2013
DOIs
Publication statusPublished - Apr 2014

Fingerprint

Cell Adhesion
Contractility
Cytoskeleton
Stress Fibers
Actin
Cell adhesion
Elasticity
Numerical Investigation
Actin Cytoskeleton
Focal Adhesions
Substrate
Fiber
Adhesion
Fibers
Cell
Substrates
Stiffness
Dependent
Cell Shape
Predict

Keywords

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

ASJC Scopus subject areas

  • Biotechnology
  • Mechanical Engineering
  • Modelling and Simulation
  • Medicine(all)

Cite this

Cellular contractility and substrate elasticity : A numerical investigation of the actin cytoskeleton and cell adhesion. / Ronan, William; Deshpande, Vikram S.; McMeeking, Robert M.; McGarry, J. Patrick.

In: Biomechanics and Modeling in Mechanobiology, Vol. 13, No. 2, 04.2014, p. 417-435.

Research output: Contribution to journalArticle

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