CAREER: Effect of Inflammation on Biomechanical Properties of Intervertebral Disc Cells

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The research objective of this Faculty Early Career Development (CAREER) award is to understand how inflammation directly alters the biomechanical properties and deformational behavior of cells in the intervertebral disc, independently of changes to the tissue integrity. Our aims address a critical gap in knowledge by utilizing tools of biomechanics, cell and molecular biology. Our approach will identify the effects of inflammation on the cytoskeleton and single cell mechanical and swelling properties of nucleus pulposus cells. Multi-scale cellular deformation will also be measured in-situ. Our approach will investigate the responses of nucleus pulposus cells to inflammation triggered by a single or multiple inflammatory mediators, and compared to responses of cells treated with anti-inflammatory agents.If successful, these studies would add significantly to the field's understanding of the direct effects of inflammation on cell mechanics and function. Our findings may identify biomechanical mediators of inflammatory changes, advancing our understanding of how inflammation propagates the positive feedback cascade during degeneration, independently of changes to disc tissue integrity. Our studies on cellular behavior can advance the diagnostic or treatment of disc degeneration by identifying criteria for mitigating biomechanical alterations due to inflammation. The educational plan focuses on the introduction of mechanobiology into our graduate curriculum to strengthen a program that is grounded in molecular studies. In addition, two educational programs are proposed to broaden the participation of underrepresented groups in science. A basic science curriculum is proposed for the Medical Scholars Pipeline Program, a 5-year longitudinal outreach program for preparing high school students from underrepresented groups for careers in healthcare, biomedical science and engineering. A new mentoring organization is also proposed for leadership development and career advancement of female students and faculty in biomedical science and engineering.