Soft tissues in the human body consist of cells living in a matrix of large proteins and other biomolecules. The mechanical behavior of the matrix is important to how tissues and organs function. The mechanical properties of the matrix are governed by complex structures formed by the protein collagen. However, collagen structures can change in response to mechanical forces, such as those that occur during exercise or as part of disease progression. This project combines mathematical modeling with experiments on a model tissue system to study how collagen structures change under externally applied forces and forces exerted by the cells. The new understanding gained from this project will advance knowledge of collagen biomechanics and cell mechanobiology. This will advance the nation?s health and welfare through translation to the study of diseases, and by enabling new therapeutic strategies to address pathological changes in tissue structure. An important outcome of the project will be interdisciplinary research training for graduate students and undergraduates to prepare them for careers in academia and industry. The project will also provide research internships for Baltimore City high school students that will help increase of diversity in the technical workforce in engineering and science.

This project is an integrated micromechanical experimental and modeling program to investigate the role and interactions of collagen mechanochemistry, mechanosensitive cellular contraction, and mechanosensitive collagen production on the growth and remodeling of the extracellular matrix. The project will (i) develop a microtissue experimental system to measure the effects of global mechanical stimuli on growth and remodeling as well as mechanochemical effects on collagen structure; (ii) develop a micromechanical model for collagen tissue growth and remodeling based on the fibril-level processes of concurrent collagen deposition and degradation including effects of mechanochemistry and cellular contraction; and (iii) investigate effects of cell-scale perturbations on collagen growth and remodeling. The integrated modeling and experimental framework will allow separate characterization of mechanical stimulation of collagen mechanochemistry, collagen production, and cellular contraction, and evaluation of their long-term effects on tissue growth, remodeling of collagen structure and tissue properties, and homeostasis. The local perturbation studies will examine the complicated interplay between the remodeling of collagen fiber structures and cellular actin stress fiber structures. New fundamental understanding gained from this project will lead to the development of more mechanistic and predictive models for collagen growth and remodeling that will find application in both the study of mechanically implicated diseases and in tissue engineering.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

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Johns Hopkins University
United States
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