CAREER: Elucidation of the Physical Principles the Govern Endothelial Structure and Function

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This Faculty Early Career Development (CAREER) award will utilize principles from cell biology and mechanics to establish the role that biomechanical forces and fluid forces play in the structure and function of the endothelium. Endothelial cells line the inside of all blood and lymphatic vessels within the body. Their ability to regulate structure and function is essential to proper functioning of every major organ within the body. Furthermore, aberrant endothelial cell function has been linked to debilitating diseases including atherosclerosis, cardiac fibrosis, thrombosis, and brain tumors. Endothelial cells are constantly exposed to biomechanical inputs, but the influence mechanics has on their ability to regulate structure and function is not well understood. Specifically their ability to change phenotype (plasticity) is a gap in our understanding. To fill this gap, this project will: 1) develop an endothelial biomechanical force model; 2) define the role of fluid shear stress and cell-derived mechanical forces on endothelial permeability; and 3) Investigate the influence of fluid pressure and fluid frequency on endothelial permeability. The education and outreach initiatives of this program will train and mentor STEM majors of the future through utilization the Research and Mentoring Program (RAMP), McNair Scholars Program, and Campus Connect program at the University of Central Florida. Collaboration with the programs mentioned above will provide an opportunity for high school, undergraduate, and graduate students from underrepresented groups to receive hands-on training and research experience. This work will address the central hypothesis that hemodynamic forces and cell-derived biomechanical forces interact synergistically to influence endothelial structure and function. In support of this research objective this work will 1) define the role of angioadaptation in endothelial plasticity; 2) define the role of fluid shear stress and intercellular stress on endothelial permeability; and 3) investigate the influence of fluid pressure and fluid frequency on endothelial permeability. To complement the research objectives of this program the outreach objectives are to: 1) engage the STEM majors of the future; 2) energize the STEM majors of the future; and 3) educate the STEM majors of the future. Every major organ in the body requires endothelial cells to maintain homeostasis. Therefore, this program will be applicable to numerous vascular systems such as the cardiovascular system and cerebrovascular system. The results of this work have the potential to advance knowledge in endothelial biology, biomechanics, and the drug delivery fields.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.