Modeling Mechanical Cell-Matrix Interactions in Articular Cartilage

North Carolina State University, Raleigh NC

Investigators

Abstract

Haider 0211154 The investigator is developing multiphasic models for mechanical interactions between the cells and extracellular matrix in articular cartilage. A combination of analytical and numerical methods are used to solve: (1) contact problems that model experiments used to determine mechanical properties of isolated cell (chondrocyte) and cell-matrix (chondron) units, (2) interface problems that model local cell-matrix mechanics of the chondron in vivo, and (3) fast boundary integral models for transmission of mechanical signals in a tissue layer populated with many cells. Through collaboration with an orthopaedic research lab, the models developed by the investigator are being applied to: (a) the determination of material properties of cell and tissue explants using in-vitro micropipette testing and video microscopy, and (b) the simulation of local cell-matrix mechanics and comparison to confocal microscopy of dynamic loading in a tissue layer. A fundamental goal of this project is to quantify the dependence of local cell mechanics on external loading. By correlating experimental measurements of cell metabolic activity to mechanical components of the local cell environment, the complex relationship between tissue metabolism and cell mechanics is analyzed. Variations in chondron material and geometric properties, within and across a variety of tissue populations, are also incorporated into the models. This project contributes to understanding of the role of mechanics in maintenance of the extracellular matrix, and associated matrix degeneration with aging due to osteoarthritis. Articular cartilage is the primary load-bearing tissue in joints such as the knee, shoulder and hip. Degeneration of cartilage leads to osteoarthritis, a painful condition that affects millions of Americans and is predominantly associated with aging. Under repeated loading, the structural matrix of cartilage is in a continual state of turnover that is regulated by specialized cells called chondrocytes. These cells synthesize matrix components yet, remarkably, have no neural connection to the brain. As a result, cell metabolic activities directed at repairing the structural matrix are highly dependent on the local cell environment. In this project, a mathematical modeler collaborates with an orthopaedic research lab to understand the role of mechanical forces in the maintenance of cartilage. At the cellular level, forces in cartilage result from a complex coupling of solid and fluid mechanics with energy dissipation. Results of this work predict the dependence of local forces at the cellular scale on external loading. Local force predictions facilitate a quantitative description of the complex relationship between cell metabolic activity and cell mechanics. In conjunction with associated experiments for a variety of tissue populations, the models lead to an understanding of how these remarkable cells can maintain cartilage over the course of a lifetime, and how structural degeneration of cartilage is initiated in osteoarthritis.