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

这个学院早期职业发展（Career）奖将利用细胞生物学和力学的原理来建立生物力学力和流体力在内皮结构和功能中的作用。内皮细胞排列在体内所有血液和淋巴管的内部。它们调节结构和功能的能力对身体内每个主要器官的正常运作至关重要。此外，内皮细胞功能异常与衰弱性疾病有关，包括动脉粥样硬化、心脏纤维化、血栓形成和脑肿瘤。内皮细胞不断暴露于生物力学输入，但力学对其调节结构和功能的能力的影响尚不清楚。具体来说，它们改变表型（可塑性）的能力是我们理解中的一个空白。为了填补这一空白，本项目将：1)建立内皮生物力学力模型；2)定义流体剪切应力和细胞源性机械力对内皮细胞渗透性的作用；3)研究流体压力和流体频率对内皮细胞通透性的影响。该计划的教育和推广计划将通过利用中佛罗里达大学的研究和指导计划（RAMP）、麦克奈尔学者计划和校园连接计划，培训和指导未来的STEM专业学生。与上述项目的合作将为来自代表性不足群体的高中生、本科生和研究生提供获得实践培训和研究经验的机会。这项工作将解决血流动力学力和细胞来源的生物力学力协同作用影响内皮结构和功能的中心假设。为了支持这一研究目标，本研究将1)确定血管适应在内皮细胞可塑性中的作用；2)明确流体剪切应力和细胞间应力对内皮细胞通透性的影响；3)研究流体压力和流体频率对内皮细胞通透性的影响。为了补充该计划的研究目标，外展目标是：1)吸引未来的STEM专业学生；2)激励未来STEM专业的学生；3)培养未来的STEM专业学生。身体的每个主要器官都需要内皮细胞来维持体内平衡。因此，该方案将适用于众多血管系统，如心脑血管系统。这项工作的结果有可能推进内皮生物学，生物力学和药物输送领域的知识。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.