title: The effect of matrix tension-compression nonlinearity and fixed negative charges on chondrocyte responses in cartilage.
abstract: Thorough analyses of the mechano-electrochemical interaction between articular cartilage matrix and the chondrocytes are crucial to understanding of the signal transduction mechanisms that modulate the cell metabolic activities and biosynthesis. Attempts have been made to model the chondrocytes embedded in the collagen-proteoglycan extracellular matrix to determine the distribution of local stress-strain field, fluid pressure and the time-dependent deformation of the cell. To date, these models still have not taken into account a remarkable characteristic of the cartilage extracellular matrix given rise from organization of the collagen fiber architecture, now known as the tension-compression nonlinearity (TCN) of the tissue, as well as the effect of negative charges attached to the proteoglycan molecules, and the cell cytoskeleton that interacts with mobile ions in the interstitial fluid to create osmotic and electro-kinetic events in and around the cells. In this study, we proposed a triphasic, multi-scale, finite element model incorporating the Conewise Linear Elasticity that can describe the various known coupled mechanical, electrical and chemical events, while at the same time representing the TCN of the extracellular matrix. The model was employed to perform a detailed analysis of the chondrocytes' deformational and volume responses, and to quantitatively describe the mechano-electrochemical environment of these cells. Such a model describes contributions of the known detailed micro-structural and composition of articular cartilage. Expectedly, results from model simulations showed substantial effects of the matrix TCN on the cell deformational and volume change response. A low compressive Poisson's ratio of the cartilage matrix exhibiting TCN resulted in dramatic recoiling behavior of the tissue under unconfined compression and induced significant volume change in the cell. The fixed charge density of the chondrocyte and the pericellular matrix were also found to play an important role in both the time-dependent and equilibrium deformation of the cell. The pericellular matrix tended to create a uniform osmolarity around the cell and overall amplified the cell volume change. It is concluded that the proposed model can be a useful tool that allows detailed analysis of the mechano-electrochemical interactions between the chondrocytes and its surrounding extracellular matrix, which leads to more quantitative insights in the cell mechano-transduction.
authors.affiliation: Department of Biomedical Engineering, Columbia University, 351 Engineering Terrace 500 West 120th Street, New York, NY 10027, USA.
authors.forename: Morakot
authors.initials: M
authors.lastname: Likhitpanichkul
authors.forename: X Edward
authors.initials: XE
authors.lastname: Guo
authors.forename: Van C
authors.initials: VC
authors.lastname: Mow
mesh_terms: D000818:Animals; D002356:Cartilage / Q000737:chemistry* / Q000378:metabolism; D019902:Chondrocytes / Q000737:chemistry* / Q000378:metabolism*; D019245:Compressive Strength; D005109:Extracellular Matrix / Q000737:chemistry* / Q000378:metabolism; D020342:Finite Element Analysis; D008954:Models, Biological; D017711:Nonlinear Dynamics; D011509:Proteoglycans / Q000737:chemistry; D055672:Static Electricity; D013718:Tensile Strength; D016474:Weight-Bearing
chemical_list: D011509:Proteoglycans