Micromechanical Model of Effects of Matrix Viscoelasticity on Cell Contractility in Collagenous Tissues

The mechanical behavior of collagen tissue constructs is determined by the structure and properties of the collagen fibers and active cellular contraction. The anisotropic structure of cellular stress fibers and collagen fibers remodel in response to mechanical loads. This study expands upon previously developed micromechanical constitutive models of collagen tissues to incorporate tissue viscoelasticity and investigate the mechanosensitive active cellular response. We fit the model parameters against experiments of Triton X-100 treated microtissues with lysed/inactive cells. We then validate the model prediction against the response of a 3D microtissue with active cellular contraction, to investigate the effect of mechanical loading on the behavior of the cells. The model accurately predicts the rate-dependent load-unload response of an untreated tissue and displays hysteresis during the load-unload. This integrated experimental modeling approach allows us to decouple the cell and matrix mechanics, and to identify their respective contributions to the tissue's stress response. Effects of matrix viscoelasticity on cell contractility will be discussed. Future studies will extend the model to include a fiber-level description of collagen growth, remodeling, and degradation.