Measurement of In Situ Mechanical Forces During Neotissue Formation

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This grant will use tiny force sensors to measure the forces that exist during the earliest stages of tissue formation and for the maturation stages that follow. The push and pull of cells on each other are a critical part of biological development and tissue formation. This is particularly true for the growth of muscles, bones, and connective tissues in our bodies. Cells are stimulated by these local forces, responding in ways that help create the complex structures needed for more mature tissues to function properly. Direct measurement of cellular-scale forces is difficult, particularly in cell-dense, 3D samples. The information gained from this work will fill a knowledge gap in developmental biology and tissue regeneration. The research team will include a diverse group of undergraduate and graduate students, in addition to local public school teachers, who will be central to our outreach efforts in communicating the importance of interdisciplinary research to high school students.To accomplish our goals, two objectives have been established. First, we will determine how the physical characteristics of our cellular-scale force probes influence measurements in a model system of tissue formation. This includes the size, stiffness, and chemical coating of the probes. Second, we will investigate how local mechanical forces change over time as cartilage-like and tendon/ligament-like neotissues form and mature. These studies will provide completely new insight on the relevance of forces in cell-dense biological structures, benefiting fields as diverse as developmental biology and 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.