Computational Modeling of Developing Cartilage Using Experimentally Derived Geometries and Compressive Moduli

Abstract

During chondrogenesis, tissue organization changes dramatically. We previously showed that the compressive moduli of chondrocytes increase concomitantly with extracellular matrix (ECM) stiffness, suggesting cells were remodeling to adapt to the surrounding environment. Due to the difficulty in analyzing the mechanical response of cells in situ, we sought to create an in silico model that would enable us to investigate why cell and ECM stiffness increased in tandem. The goal of this study was to establish a methodology to segment, quantify, and generate mechanical models of developing cartilage to explore how variations in geometry and material properties affect strain distributions. Multicellular geometries from embryonic day E16.5 and postnatal day P3 murine cartilage were imaged in three-dimensional (3D) using confocal microscopy. Image stacks were processed using matlab to create geometries for finite element analysis using ANSYS. The geometries based on confocal images and isolated, single cell models were compressed 5% and the equivalent von Mises strain of cells and ECM were compared. Our simulations indicated that cells had similar strains at both time points, suggesting that the stiffness and organization of cartilage changes during development to maintain a constant strain profile within cells. In contrast, the ECM at P3 took on more strain than at E16.5. The isolated, single-cell geometries underestimated both cell and ECM strain and were not able to capture the similarity in cell strain at both time points. We expect this experimental and computational pipeline will facilitate studies investigating other model systems to implement physiologically derived geometries.