CAREER: Combinatorial Biomaterials for Endothelial Cell Mechanobiology

由南佛罗里达大学材料研究部生物材料项目颁发的CAREER奖旨在研究模拟基底基质机械和化学特性的组合生物材料，用于内皮细胞机械转导的高通量研究。内皮细胞通过附着在基底层并组织成单层，形成血管和其他组织的内层。由于这些特化组织的微环境复杂，机械转导（将机械输入转化为生化信号）机制是调节内皮细胞稳态和向疾病状态发展的核心。在内皮细胞力学生物学中，组合方法能够准确地概括自然生理学的范围，并快速分析多种基质介导的机械和化学信号的相互作用。本文提出的研究计划的预期结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相结合的理解的空白。同时，基于机械转导的基本生物物理原理的实践教程将为高中生物医学科学课程开发，旨在鼓励STEM学科的多样性。这些教程将由一个由高中学生和教师组成的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交付。拟议的研究和推广活动将为学生提供与来自不同学科的研究人员互动的机会，并与社区分享他们的研究。内皮细胞在一层薄薄的蛋白质基质上组织，形成了体内每条血管的内膜。目前的提案整合了研究和教育活动，旨在调查指导这些特化组织的调节和疾病进展的复杂信号集。具体来说，将研究由血流和组织刚度引起的力的机械转导（将机械输入转化为生化信号的过程）的机制。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，并有望提供对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成为可能，这些材料可以模板结构，并指导工程组织中的组织进行修复和替换。基于本研究阐明的机械转导原理的实践教程将为高中生物医学科学课程开发，旨在鼓励STEM学科的多样性。这些教程将由一个由高中学生和教师组成的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交付。这种合作学习方法将提高学生在多个层面的训练。

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.