Modeling Mechanical Cell-Matrix Interactions in Articular Cartilage

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Haider0211154 The investigator is developing multiphasic models formechanical interactions between the cells and extracellularmatrix in articular cartilage. A combination of analytical andnumerical methods are used to solve: (1) contact problems thatmodel experiments used to determine mechanical properties ofisolated cell (chondrocyte) and cell-matrix (chondron) units, (2)interface problems that model local cell-matrix mechanics of thechondron in vivo, and (3) fast boundary integral models fortransmission of mechanical signals in a tissue layer populatedwith many cells. Through collaboration with an orthopaedicresearch lab, the models developed by the investigator are beingapplied to: (a) the determination of material properties of celland tissue explants using in-vitro micropipette testing and videomicroscopy, and (b) the simulation of local cell-matrix mechanicsand comparison to confocal microscopy of dynamic loading in atissue layer. A fundamental goal of this project is to quantifythe dependence of local cell mechanics on external loading. Bycorrelating experimental measurements of cell metabolic activityto mechanical components of the local cell environment, thecomplex relationship between tissue metabolism and cell mechanicsis analyzed. Variations in chondron material and geometricproperties, within and across a variety of tissue populations,are also incorporated into the models. This project contributesto understanding of the role of mechanics in maintenance of theextracellular matrix, and associated matrix degeneration withaging due to osteoarthritis. Articular cartilage is the primary load-bearing tissue injoints such as the knee, shoulder and hip. Degeneration ofcartilage leads to osteoarthritis, a painful condition thataffects millions of Americans and is predominantly associatedwith aging. Under repeated loading, the structural matrix ofcartilage is in a continual state of turnover that is regulatedby specialized cells called chondrocytes. These cells synthesizematrix components yet, remarkably, have no neural connection tothe brain. As a result, cell metabolic activities directed atrepairing the structural matrix are highly dependent on the localcell environment. In this project, a mathematical modelercollaborates with an orthopaedic research lab to understand therole of mechanical forces in the maintenance of cartilage. Atthe cellular level, forces in cartilage result from a complexcoupling of solid and fluid mechanics with energy dissipation.Results of this work predict the dependence of local forces atthe cellular scale on external loading. Local force predictionsfacilitate a quantitative description of the complex relationshipbetween cell metabolic activity and cell mechanics. Inconjunction with associated experiments for a variety of tissuepopulations, the models lead to an understanding of how theseremarkable cells can maintain cartilage over the course of alifetime, and how structural degeneration of cartilage isinitiated in osteoarthritis.