The effect of remodelling and contractility of the actin cytoskeleton on the shear resistance of single cells: A computational and experimental investigation

Enda P. Dowling, William Ronan, Gidon Ofek, Vikram S. Deshpande, Robert M. McMeeking, Kyriacos A. Athanasiou, J. Patrick McGarry

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

The biomechanisms that govern the response of chondrocytes to mechanical stimuli are poorly understood. In this study, a series of in vitro tests are performed, in which single chondrocytes are subjected to shear deformation by a horizontally moving probe. Dramatically different probe force-indentation curves are obtained for untreated cells and for cells in which the actin cytoskeleton has been disrupted. Untreated cells exhibit a rapid increase in force upon probe contact followed by yielding behaviour. Cells in which the contractile actin cytoskeleton was removed exhibit a linear force-indentation response. In order to investigate the mechanisms underlying this behaviour, a three-dimensional active modelling framework incorporating stress fibre (SF) remodelling and contractility is used to simulate the in vitro tests. Simulations reveal that the characteristic force-indentation curve observed for untreated chondrocytes occurs as a result of two factors: (i) yielding of SFs due to stretching of the cytoplasm near the probe and (ii) dissociation of SFs due to reduced cytoplasm tension at the front of the cell. In contrast, a passive hyperelastic model predicts a linear force-indentation curve similar to that observed for cells in which the actin cytoskeleton has been disrupted. This combined modelling-experimental study offers a novel insight into the role of the active contractility and remodelling of the actin cytoskeleton in the response of chondrocytes to mechanical loading.

Original languageEnglish (US)
Pages (from-to)3469-3479
Number of pages11
JournalJournal of the Royal Society Interface
Volume9
Issue number77
DOIs
StatePublished - Dec 7 2012

Keywords

  • Actin cytoskeleton
  • Cell contractility
  • Cell mechanics
  • Chondrocyte
  • Finite element
  • In vitro shear

ASJC Scopus subject areas

  • Biophysics
  • Biotechnology
  • Bioengineering
  • Biomedical Engineering
  • Biomaterials
  • Biochemistry

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