CAREER: Studying Tendon Cell Mechanobiology in the Native Tissue Environment

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This Faculty Early Career Development (CAREER) grant supports research to identify how the behavior of cells within tendons is affected by tissue damage and how this leads to tendon degeneration. Previous work studied the response of tendon cells to different strains under artificial conditions. However, it is important to understand how cells response to damage inside the native tendon tissue. This is because many important interactions are lost when cells are isolated from their native environment. Also, these interactions between cells and their environment have a strong effect on cell behavior. Therefore, this project will develop novel techniques to study cell behavior in their native tissue environment. These techniques will be used to understand how tendon fatigue damage causes tendon degeneration. This information will provide the scientific foundation for developing new treatments for tendon disorders. Also, engineering students will help incorporate our results into high school biology classes. We will identify whether this improves the recruitment and retention of more women in engineering.The research goals of this CAREER project are to determine how tendon cells sense physical stimuli in the native tissue environment and to identify the role of dysfunctional cell mechanobiology in tendon degeneration. The central hypothesis is that fatigue damage alters the physical stimuli presented in situ to cells within tendon and that mechanotransduction of these altered stimuli initiates the negative cellular response leading to tendon degeneration. To test this hypothesis, the researchers will develop a live tissue explant model enabling simultaneous in situ measurement of local physical stimuli and gene expression and will identify the mechanotransduction mechanisms that drive the response of tendon cells to mechanical loading within the native tissue environment. The innovative technique of colocalizing fatigue damage (i.e., altered strains and collagen organization) with cellular gene expression will identify the specific physical stimuli that initiate tissue degeneration in the native tendon environment. Importantly, the explant model also enables the researchers to perturb mechanotransduction signaling pathways during fatigue loading and investigate their mechanistic role in inducing tendon degeneration. Beyond tendon, by investigating whether canonical mechanotransduction mechanisms observed in 2D also operate within tissue explants, this work will advance the broad understanding of how cells within fibrous soft tissues (e.g., tendon, meniscus, skin) respond to physical stimuli in the native tissue environment.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.