Influence of Spreading and Contractility on Cell Detachment
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Cell adhesion is a key phenomenon that affects fundamental cellular processes such as morphology, migration, and differentiation. In the current study, an active modelling framework incorporating actin cytoskeleton remodelling and contractility, combined with a cohesive zone model to simulate debonding at the cell–substrate interface, is implemented to investigate the increased resistance to detachment of highly spread chondrocytes from a substrate, as observed experimentally by Huang et al. (J. Orthop. Res. 21: 88–95, 2003). 3D finite element meshes of the round and spread cell geometries with the same material properties are created. It is demonstrated that spread cells with a flattened morphology and a larger adhesion area have a more highly developed actin cytoskeleton than rounded cells. Rounded cells provide less support for tension generated by the actin cytoskeleton; hence, a high level of dissociation is predicted. It is revealed that the more highly developed active contractile actin cytoskeleton of the spread cell increases the resistance to shear deformation, and subsequently increases the shear detachment force. These findings provide new insight into the link between cell geometry, cell contractility, and cell–substrate detachment.
KeywordsActin cytoskeleton Chondrocyte Cartilage Finite element modelling Cell mechanics In vitro shear Cell adhesion
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 wish to acknowledge the SFI/HEA Irish Centre for High-End Computing (ICHEC) for the provision of computational facilities and support. The authors would like to thank Prof. K.A. Athanasiou, Prof. V.S. Deshpande, Prof. R.M. McMeeking, and Dr. W. Ronan for helpful discussions and insights relating to this study.
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