CAREER: Combinatorial Biomaterials for Endothelial Cell Mechanobiology

职业：内皮细胞力学生物学的组合生物材料

• 批准号: 1056475
• 负责人: Nathan Gallant
• 金额: $ 50万
• 依托单位: University of South Florida
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2017-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1056475&HistoricalAwards=false
• 关键词: CAREER; Combinatorial; Biomaterials; Endothelial; Cell

This CAREER award by the Biomaterials program in the Materials Research Division to University of South Florida is to study combinatorial biomaterials that mimic the mechanical and chemical properties of the basement matrix for high throughput studies of endothelial cell mechanotransduction. Endothelial cells form the lining of blood vessels and other tissues by adhering to the basal lamina and organizing into monolayers. Due to the complex microenvironment of these specialized tissues, mechanotransduction (translation of mechanical inputs into biochemical signals) mechanisms are central to regulating endothelial cell homeostasis and progression towards disease states. A combinatorial approach is uniquely able to accurately recapitulate the range of natural physiology and rapidly analyze the interactions of multiple matrix-mediated mechanical and chemical signals in endothelial cell mechanobiology. The expected outcomes of the research program proposed here will provide the necessary tools and fill the gap in the current understanding of how mechanical properties and forces are sensed, translated into biochemical signals, and integrated with other pathways that control endothelial cell fate. Concurrently, hands-on tutorials, based on the underlying biophysical principles of mechanotransduction, will be developed for a high school Biomedical Sciences curriculum expected to encourage diversity in STEM disciplines. These tutorials will be designed and delivered by a team of high school students and teachers collaborating with University of South Florida faculty and graduate and undergraduate students. The proposed research and outreach activities will provide students opportunities to interact with researchers from a variety of disciplines and share their research with the community.Endothelial cells organize on a thin protein matrix and form the lining of every blood vessel in the body. The present proposal integrates research and education activities designed to investigate the complex set of signals that direct the regulation and disease progression of these specialized tissues. Specifically, mechanisms of mechanotransduction (the process of translating mechanical inputs into biochemical signals) from forces caused by blood flow and tissue stiffness will be studied. A combinatorial approach will be used which enables high throughput studies to rapidly analyze the interactions of multiple mechanical and chemical signals. These studies will develop new combinatorial materials and are expected to provide an understanding of how mechanical properties and forces control endothelial cell behavior. Furthermore, the findings of this work will enable the design of materials that template the structure and guide the organization in engineered tissues for repair and replacement. Hands-on tutorials, based on the principles of mechanotransduction elucidated by this research, will be developed for a high school Biomedical Sciences curriculum expected to encourage diversity in STEM disciplines. These tutorials will be designed and delivered by a team of high school students and teachers collaborating with University of South Florida faculty and graduate and undergraduate students. This collaborative learning approach will enhance the training of students across multiple levels.

该职业奖由南佛罗里达大学材料研究部的生物材料项目授予，旨在研究模拟基底基质机械和化学性质的组合生物材料，用于内皮细胞机械转导的高通量研究。内皮细胞通过粘附于基底层并组织成单层而形成血管和其他组织的衬里。 由于这些特化组织的复杂微环境，机械转导（将机械输入翻译成生化信号）机制对于调节内皮细胞稳态和向疾病状态的进展至关重要。一种组合方法是唯一能够准确地概括自然生理学的范围，并快速分析内皮细胞机械生物学中多种基质介导的机械和化学信号的相互作用。这里提出的研究计划的预期成果将提供必要的工具，并填补目前对机械特性和力如何被感知、转化为生化信号以及与控制内皮细胞命运的其他途径整合的理解中的差距。 同时，将根据机械传导的基本生物物理原理为高中生物医学科学课程开发实践教程，以鼓励STEM学科的多样性。这些教程将由一个高中学生和教师团队与南佛罗里达大学的教师、研究生和本科生合作设计和提供。建议的研究和外展活动将为学生提供机会，与来自不同学科的研究人员互动，并与社区分享他们的研究成果。内皮细胞在薄的蛋白质基质上组织，形成体内每一根血管的衬里。 本提案整合了研究和教育活动，旨在调查指导这些专门组织的调节和疾病进展的复杂信号集。具体而言，将研究由血流和组织硬度引起的力的机械转导机制（将机械输入转化为生化信号的过程）。将使用组合方法，使高通量研究能够快速分析多种机械和化学信号的相互作用。这些研究将开发新的组合材料，并有望提供机械性能和力如何控制内皮细胞行为的理解。此外，这项工作的发现将使材料的设计，模板的结构和指导组织的工程组织的修复和更换。基于这项研究阐明的机械传导原理，将为高中生物医学科学课程开发实践教程，以鼓励STEM学科的多样性。这些教程将由一个高中学生和教师团队与南佛罗里达大学的教师、研究生和本科生合作设计和提供。这种协作学习方法将加强对多层次学生的培训。