In-situ measurements of chondrocyte deformation under transient loading

Abstract

Chondrocytes are responsible for the elaboration and maintenance of the extracellular (EC) matrix in articular cartilage, and previous studies have demonstrated that mechanical loading modulates the biosynthetic response of chondrocytes in cartilage explants. The goal of this study is to investigate the deformation behaviour of the chondrocyte and its microenvironment under transient loading, in order to address the relationship between the applied dynamic deformation and cellular strain. In situ strain measurements were performed on cells in the middle (MZ) zone at early time points during ramp loading and at equilibrium. In this study, we characterized the behaviour of cartilage at the zonal and cellular levels under compressive loading using digital image analysis on miniature samples tested in a custom microscopy-based loading device. The experimental results indicate that significant strain amplification occurs in the microenvironment of the cell, with the minimum (compressive) principal strain found to be nearly 7X higher in the intracellular region (IC), and ~5X higher in the pericellular (PC) matrix than in the EC matrix at peak ramp. A similar strain amplification mechanism was observed in the maximum (tensile) principal strain, and this behaviour persisted even after equilibrium was reached. The experimental results of this study were interpreted in the context of a finite element model of chondrocyte deformation, which modelled the cell as a homogeneous gel, possessing either a spherical or ellipsoidal geometry, surrounded by a semi permeable membrane, and accounted for the presence of a PC matrix. The results of the FEA demonstrate significant strain amplification mechanism in the IC region, greater than had previously been suggested in earlier computational studies of cell-EC matrix interactions. Based on the FEA, this outcome is understood to result from the large disparity between EC matrix and intracellular properties. The results of this study suggest that mechanotransduction of chondrocytes may be significantly mediated by this strain amplification mechanism during loading.

A biphasic multiscale study of the mechanical microenvironment of chondrocytes within articular cartilage under unconfined compression

“…8), which is consistent with previous computational (Alexopoulos et al, 2005; Baer et al, 2003; Han et al, 2007; Julkunen et al, 2009; Kim et al, 2008; Korhonen and Herzog, 2008; Wu and Herzog, 2006) and experimental studies (Chahine et al, 2007; Choi et al, 2007; Upton et al, 2008). The magnitude of the strain amplification was about 3, which was within the range of 2–7 reported in previous studies of static loading (Alexopoulos et al, 2005; Chahine et al, 2007). During dynamic loading the strain amplification can be as high as 20 (Kim et al, 2008).…”

“…While this assumption is consistent with most previous computational studies, clearly the shape of the chondrocytes is zone dependent. Several computational studies of chondrocytes in the axisymmetric axis of the macroscale model reported that chondrocyte geometry affected the local deformation behavior in and around the chondrocyte (Baer et al, 2003; Chahine et al, 2007). In the future, it would be of interest to study the effect of chondrocyte shape on their mechanical behavior in different zonal and radial locations.…”

Multiscale cartilage biomechanics: technical challenges in realizing a high-throughput modelling and simulation workflow

“…The representative volume should also be large enough to include characteristic geometrical features of the region's cellular organization. Traditionally, computational simulations of chondrocytes used models with an edge length of 100 mm [49], originated from the study by Guilak & Mow [46]. This model and its successors placed a single chondron at the centre of the modelling volume, commonly overlooking the actual cell density of the cartilage zone.…”

Computational modeling of cell mechanics

“…Simulations of this model and its derivatives have been particularly useful in determining the mechanics of chondrons Haider, 2004; Alexopoulos et al ., 2005;Korhonen et al ., 2006Chahine et al ., 2007;Kim et al ., 2008Kim et al ., , 2010 (Fig. 4.11).…”