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

本学院早期职业发展（Career）奖的研究目标是了解炎症如何直接改变椎间盘细胞的生物力学特性和变形行为，而不影响组织完整性的变化。我们的目标是通过利用生物力学，细胞和分子生物学的工具来解决知识上的关键差距。我们的方法将确定炎症对髓核细胞的细胞骨架和单细胞机械和肿胀特性的影响。多尺度细胞变形也将在现场测量。我们的方法将研究髓核细胞对由单一或多种炎症介质引发的炎症的反应，并与抗炎剂处理的细胞的反应进行比较。如果成功，这些研究将大大增加该领域对炎症对细胞力学和功能的直接影响的理解。我们的研究结果可能确定炎症变化的生物力学介质，促进我们对退变期间炎症如何传播正反馈级联的理解，而不依赖于椎间盘组织完整性的变化。我们对细胞行为的研究可以通过确定减轻炎症引起的生物力学改变的标准来推进椎间盘退变的诊断或治疗。教育计划的重点是将机械生物学引入我们的研究生课程，以加强以分子研究为基础的课程。此外，还提出了两项教育计划，以扩大代表性不足的群体对科学的参与。医学学者管道项目（Medical Scholars Pipeline Program）是一个为期5年的纵向拓展项目，旨在帮助来自代表性不足群体的高中学生为医疗保健、生物医学科学和工程领域的职业做好准备。此外，还建议建立一个新的指导组织，以促进生物医学科学与工程专业女学生和女教师的领导力发展和职业发展。

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.