Reconstituted Tissue Mechanics

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DESCRIPTION (VERBATIM): The long-range goal of this work is to characterize the relationship between structure and mechanical function in biological tissues, e.g., connective tissue or muscle. Models of these tissues are assembled from cells and extracellular matrix components. The model tissues provide simplified systems in which the cellular and matrix composition can be varied, the organization of cell and matrix components can be visualized by microscopy, and the contractile force exerted by the cells and the stiffness of the tissue can be readily measured. The project is motivated by the hypothesis that the intrinsic mechanical properties of the constituent cells and of the matrix and the interactions of cells with each other and with the matrix determine the mechanical properties of the tissue, including stiffness and contractile force. The specific aims are to determine the contributions to the mechanics of the model tissues of the cellular cytoskeletons and the collagen matrix, and of integrin-mediated interactions of the cells with the matrix and of cadherin-mediated interactions of the cells with each other. The effects of selective perturbation of these structures on the organization and mechanical properties of the tissue models will be measured. The results will be interpreted using a quantitative theoretical model by which the mechanical properties of cells and matrix can be deduced from the measurements on model tissues. This work provides a powerful and general approach to determining the mechanical functions of specific molecular components of the cells and matrix. In addition to the basic information learned about molecular function, this work provides an important foundation for the design and mechanical evaluation of tissues engineered for clinical applications.