The research objective of this Faculty Early Career Development (CAREER) award is to investigate how the cytoskeleton (internal cell scaffolding) of tendon progenitor cells regulates developing tissue mechanical properties to influence tendon formation. Tendon transmits forces from muscle to bone, and fails to regenerate when injured, often resulting in permanent orthopedic dysfunction. The premise of this study is that understanding how the tendon forms during embryonic development will advance tendon regeneration strategies. Inside all cells are cytoskeletal filaments that act as scaffolding to impart mechanical integrity to a cell, and that also sense and transmit extracellular physical forces as biological signals inside a cell. These signals can direct cells to secrete and surround themselves with matrix, from which adult tissues derive their mechanical properties. In turn, cells can sense these mechanical properties and receive new signals, and so forth. However, this scenario is less likely with embryonic tendon as the tissue is highly cellular and lower in matrix content, leading to the question of from where do mechanical cues arise during development, and how do they direct tendon formation? The goals of this project are to investigate the cytoskeleton as a significant contributor to the mechanical properties of highly cellular embryonic tendon, and to determine its role in the mechanoregulation of new tendon formation. Toward that end, this study will chemically modify the cytoskeletal network of tendon progenitor cells in both embryonic tissues and simplified 3-dimensional engineered tendons, and the resultant effects on embryonic tendon mechanical properties and new tissue formation will be assessed with engineering and biological tools.
Successful outcomes of this study would advance the field's understanding of embryonic tendon development, and significant roles the cell cytoskeleton plays in this process. Knowledge gained could lead to improved medical interventions for orthopedic disorders. Scientifically, this work could have a transformative impact across biological fields since the cytoskeleton influences important cell functions in tissue maintenance, aging and disease. The educational objectives of this award focus on the recruitment and mentorship of undergraduate engineering students as young scientists and educators, and on outreach activities to educate the public about cutting-edge research at the intersection of engineering and biology. This will be accomplished via undergraduate student-driven research projects in the laboratory, course projects in the classroom, and teaching events at the Museum of Science in Boston.
