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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.
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. 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) and Short Term Travel Fellowship (SFI-STTF)
Keyword(s): 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
Publication Date:
2016
Type: Journal article
Peer-Reviewed: Yes
Language(s): English
Contributor(s): |~|
Institution: NUI Galway
Publisher(s): The Royal Society Publishing
File Format(s): application/pdf
First Indexed: 2016-08-12 09:22:03 Last Updated: 2016-08-12 09:22:03