Chondrocyte metabolism and matrix nano-electromechanics : the response to cartilage tissue shear deformation

Thesis (Sc. D.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2002.Includes bibliographical references (leaves 160-171).Cartilage functions as a load bearing and friction reducing material in synovial joints and it is constantly exposed to in vivo loading which is coupled to electromechanical and physicochemical forces. The swelling pressure of cartilage originates from proteoglycans containing negatively charged carboxyl and sulfate groups within glycosaminoglycans. Proteoglycans are embedded within the network of collagen fibrils whose molecular structure (supercoiled helix of three alpha-chain subunits) provides resistance to tensile forces, and contributes to the overall poroviscoelastic behavior of the tissue. The dynamic balance between repulsive and tensile forces gives cartilage unique compressive and shear stiffness that varies with the rate of deformation. Chondrocytes synthesize and degrade matrix components influenced by the regulatory signals present in the extracellular matrix. The transduction mechanisms by which mechanical signals are converted to a biological response are not completely understood. Therefore, the knowledge of both biological and biophysical aspects of cartilage is important to understand the dynamic interaction between the cells and matrix. In this study, the electromechanical properties of cartilage have been studied by measuring equilibrium and dynamic shear stiffness as a function of the ionic concentration of bath solution. Measured shear properties were dependent on ionic concentration; the shear modulus increased and the phase angle between stress and strain decreased with decreasing ionic concentration.(cont.) Theoretical models were developed to interpret the experimental results: 1) the glycosaminoglycans (GAGs) were modeled as cylindrical rods (a unit cell model) with the geometry based on the experimental measurement; 2) GAGs were embedded within collagen network which supports the repulsive forces between GAGs; 3) macroscopic shear deformation was reflected on the randomly oriented unit cell; and 4) the Poisson-Boltzmann equation was used to calculate the change in the free energy and the shear modulus as a function of ionic concentration and shear deformation. The reasonable comparison between experimental results and theoretical calculations suggests that the microstructural rearrangement of GAGs during shear deformation is an important determinant in the shear stiffness of cartilage. In vivo compression of cartilage influences chondrocyte biosynthesis through mechanical deformation, fluid flow, and concomitant electrical and physicochemical changes. In vitro systems utilizing one or a combination of biophysical forces which chondrocytes are exposed to during compressive deformation in vivo have shown the complexity of biophysical environment, which potentially could alter chondrocyte biosynthesis. In this study, we have hypothesized that 1) shear deformation on poroelastic tissue like cartilage does not induce pressure gradient and relative interstitial fluid motion and 2) cell-matrix deformation produced by tissue shear deformation, with little or no accompanying fluid flow, can regulate cartilage metabolism. For this purpose, we have developed an incubator-housed tissue loading apparatus that can mimic the shear deformation in vivo on cartilage explants ex vivo ...by Moonsoo Jin.Sc.D