Influence of the extracellular matrix stiffness in tissue-engineered constructs on deformed cell shapes under large compressive deformations

Production of tissue-engineered constructs could sometimes involve delivery of compressive mechanical stimulations to the constructs in order to promote synthesis of extracellular matrix (ECM) components or cell differentiation. Here we developed a set of finite element models to determine how could the ECM/cells stiffness ratio influence the extent of shape distortions of initially round embedded cells, which has been quantified by means of the cell shape index (CSI). We found that below a 12% construct strain threshold, the ECM/cells stiffness ratio did not appear to influence the CSI and hence the extent of cellular distortion in the construct. For greater construct strains, the mean CSI of cells decreased (i.e., cells became more flattened and stretched) quadratically with the level of the global ECM-cell strain. For ECMs that were softer than the cells, the CSI decreased slightly, by no more than 0.1, even under very large construct strains (>50% strain), so a roughly round or oval cell shape was overall maintained. For stiff ECMs which were 10-times or 100-times stiffer than the embedded cells, the CSI dropped substantially with the extent of global ECM-cell strains, by up to approximately 0.4 and 0.5, respectively, so cells became considerably flattened and stretched. These data are useful for predicting cell shape distortions in construct compression experiments, where ECM/cell stiffness ratios can be empirically evaluated.