Chondrocyte damage in relation to the mechanical micro-environment of the cell

Mechanical cell damage thresholds are important parameters for numerical models that investigate cell and tissue pathologies and disease. In our current work, we investigate whether cell deformation can serve as predictor of cell damage, and how the cells mechanical environment affects cell deformations in a 3D agarose culture system. Based on earlier work, we hypothesized that cell damage 1) increases with increasing cell deformation; and 2) increases with increasing deformation duration. Finite element simulations predict that cell deformations will decrease with culture time for equal global agarose strains, because the chondrocytes produce a pericellular matrix over time that is much stiffer than the 3D agarose substrate. We therefore also hypothesize that 3) cells will deform and damage less with increasing culture times. The 3D culture was subjected to a range of deformations on a confocal microscope to investigate cell damage with real time viability staining. Histology and biochemical assays were used to quantify cell deformations and the amount of pericellular matrix over culture time. Cell viability decreased with increasing strain and with increasing strain duration. Biochemical assays showed that the amount of matrix increased over culture times; and histology showed that cells deform less with increased culture times for equal global agarose strains. Thus, the results support our hypothesis that deformation induced chondrocyte damage for equal global agarose strains increases with 1) cellular strains; and 2) duration of strains. The results further support the finite element predictions that 3) chondrocytes deform and damage less, with increasing culture times.