Influence of spreading and contractility on cell detachment.

Abstract

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.