The effect of remodelling and contractility of the actin cytoskeleton on the shear resistance of single cells: a computational and experimental investigation
Dowling, Enda P. Ronan, William Ofek, Gidon Deshpande, Vikram S. McMeeking, Robert M. Athanasiou, Kyriacos A.
Dowling, Enda P.
Ronan, William
Ofek, Gidon
Deshpande, Vikram S.
McMeeking, Robert M.
Athanasiou, Kyriacos A.
Loading...
Identifiers
http://hdl.handle.net/10379/5939
https://doi.org/10.13025/18185
https://doi.org/10.13025/18185
Repository DOI
Publication Date
2012-07-18
Keywords
Cell mechanics, Actin cytoskeleton, Cell contractility, Chondrocyte, Finite element, In vitro shear, Gene expression, Micropipette aspiration, Chondrocyte cytoskeleton, Viscoelastic properties, Mechanical compression, Articular cartilage, Agarose constructs, Confocal analysis, In vitro, Nucleus, Mechanical engineering, Biomedical engineering
Type
Article
Downloads
Citation
Dowling, Enda P., Ronan, William, Ofek, Gidon, Deshpande, Vikram S., McMeeking, Robert M., Athanasiou, Kyriacos A., & McGarry, J. Patrick. (2012). The effect of remodelling and contractility of the actin cytoskeleton on the shear resistance of single cells: a computational and experimental investigation. Journal of The Royal Society Interface, 9(77), 3469-3479. doi: 10.1098/rsif.2012.0428
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.
Funder
Publisher
The Royal Society Publishing
Publisher DOI
Rights
Attribution-NonCommercial-NoDerivs 3.0 Ireland