Previous experimental studies have determined local strain fields for both healthy and degenerate cartilage tissue during mechanical loading. However, the biomechanical response of chondrocytes in situ, in particular the response of the actin cytoskeleton to physiological loading conditions, is poorly understood. In the current study a three-dimensional (3-D) representative volume element (RVE) for cartilage tissue is created, comprising a chondrocyte surrounded by a pericellular matrix and embedded in an extracellular matrix. A 3-D active modelling framework incorporating actin cytoskeleton remodelling and contractility is implemented to predict the biomechanical behaviour of chondrocytes. Physiological and abnormal strain fields, based on the experimental study of Wong and Sah (J. Orthop. Res. 2010; 28: 1554-1561), are applied to the RVE. Simulations demonstrate that the presence of a focal defect significantly affects cellular deformation, increases the stress experienced by the nucleus, and alters the distribution of the actin cytoskeleton. It is demonstrated that during dynamic loading cyclic tension reduction in the cytoplasm causes continuous dissociation of the actin cytoskeleton. In contrast, during static loading significant changes in cytoplasm tension are not predicted and hence the rate of dissociation of the actin cytoskeleton is reduced. It is demonstrated that chondrocyte behaviour is affected by the stiffness of the pericellular matrix, and also by the anisotropy of the extracellular matrix. The findings of the current study are of particular importance in understanding the biomechanics underlying experimental observations such as actin cytoskeleton dissociation during the dynamic loading of chondrocytes. (C) 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.