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Title: In vitro Systems and Computation Models for Studying Cell-Matrix Interactions and Mechanobiology

Presented by: Edward Sander, Assoc. Professor

Roy J. Carver Department of Biomedical Engineering

ABSTRACT: During development, cell-cell and cell-matrix interactions orchestrate the formation of organized, functional tissues, but later in life these same tissues have limited capacity to regenerate themselves in response to injury, disease, or the aging process. Efforts to direct tissue self-structuring and remodeling are progressing, but they are still hampered by a lack of understanding of how these interactions are coordinated locally and globally across multiple length and times scales, particularly in terms of the role of the mechanical environment. This environment is dependent in part on the composition, organization, and stiffness of the local extracellular matrix and by the manner in which physical forces are communicated throughout the tissue to the cellular level (i.e., multi-scale mechanical interactions). This communication also involves mechanochemical interactions amongst different cell types and distinct compartments within a tissue, such as between epithelial and mesenchymal structures (EMS), which are prevalent throughout the body and are critical to tissue function. Thus, mechanical cues contribute to a complex and poorly understood process of self-structuring and remodeling that necessitates the development of a computational framework that can incorporate a multitude of different types of experiments into a comprehensive whole.

Our lab is working to build this kind of framework by utilizing in vitro time-lapse imaging experiments on keratinocytes, fibroblasts, adipocytes and other key players in the wound healing process. These experiments also inform our multi-scale computational models, which we use to understand and predict how physical forces and the mechanical interplay of cell-cell and cell-matrix interactions drives self-structuring and remodeling in healing tissues. This unique combined modeling and experimental approach will enable new insights on emergent multi-scale tissue behaviors directed by mechanobiological principles that are not possible through traditional reductionist approaches.