Cell-Matrix interactions in 3D microtissues: Multiscale mechanical models

Much of our understanding of the biological mechanisms that underlie cellular functions, such as migration, differentiation and force sensing has been garnered from studying cells cultured on two-dimensional (2D) substrates. In the recent years there has been intense interest and effort to understand cell mechanics in three-dimensional (3D) cultures, which more closely resemble the in vivo microenvironment. However, a major challenge unique to 3D settings is the dynamic feedback between cells and their surroundings. In many 3D matrices, cells remodel and reorient local extracellular microenvironment, which in turn alters the active mechanics and in many cases, the cell phenotype. Most models for matrices to date do not account for such positive feedback. Such models, validated by experiments, can provide a quantitative framework to study how injury related factors (in pathological conditions such as fibrosis and cancer metastasis) alter extracellular matrix (ECM) mechanics. They can also be used to analyze tissue morphology in complex 3D environments such as during morphogenesis and organogenesis, and guide such processes in engineered 3D tissues. In this talk, I will present discrete network simulations to study how cells remodel matrices and how this remodeling can lead to force transmission over large distances in cells[. I will also discuss an active tissue model to quantitatively study the influence of mechanical constraints and matrix stiffness on contractility and stability of micropatterned tissues.

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Vivek Shenoy, University of Pennsylvania