CAREER: Biologically Inspired Platforms: Finding The Tricks Worth Mimicking In The Extracellular Matrix

职业：受生物启发的平台：在细胞外基质中寻找值得模仿的技巧

• 批准号: 1352299
• 负责人: Delphine Gourdon
• 金额: $ 48.5万
• 依托单位: Cornell University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2017-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1352299&HistoricalAwards=false
• 关键词: CAREER; Biologically; Inspired; Platforms; Finding

Non-Technical SectionThis CAREER Award supported by the Biomaterials program in the Division of Materials Research seeks to study the structural and mechanical properties of the extracellular matrix (ECM). The extracellular matrix (ECM) is a multi-protein network used by cells to communicate with their environment. The research objectives of this Faculty Early Career Development (CAREER) project are (i) to characterize both structure and mechanics of the ECM from the protein (nanoscopic) to the cell (microscopic) level, and (ii) to exploit such fundamental understanding to engineer cell culture platforms for investigating vascularization mechanisms in functional and pathological (cancer) environments. Given the extensive interdisciplinary nature of this research, the primary educational goals of this program are to introduce students (K-12, undergraduate, and graduate) and teachers (GK-12 program) to the fields of (and the tools used in) materials and biomaterials science, biomechanics, protein physics, and cell biology. The PI will also train undergraduate and graduate students for future jobs in biomaterials science and/or engineering through (i) mentoring students from freshman to graduate level in research and (ii) integrating research into her three undergraduate and graduate level interdisciplinary courses taught across seven departments at Cornell.Technical SectionLiving cells sense and respond to their microenvironment through chemical and physical interactions determined by the adjacent cells and by the surrounding extracellular matrix (ECM) fibrillar network. The main goal of this Faculty Early Career Development (CAREER) project is to study both structural and mechanical properties of the two major building blocks of ECM structures (fibronectin and collagen) from the fiber to the cellular/tissue level. The strength of this program lies in the interdisciplinary approach that combines the PI's demonstrated expertise in (i) FRET (Fluorescence Resonance Energy Transfer) conformational mapping, and (ii) mechanical characterization of biomaterials at the nano-, and the microscopic scales. By combining these efforts, the PI will generate a fundamental understanding of the regulatory mechanisms governing ECM composition, conformation and mechanics, which will then enable the design of 2D and 3D cell culture platforms with controlled mechanobiological properties for investigating vascularization mechanisms in physiological and pathological (cancer) environments. This project has implications not only in biomaterials science but also in regenerative medicine and tissue engineering due to the fundamental role of the ECM in development and diseases such as cancer; it will also be of importance in its capacity not only to promote new approaches in cell-matrix interactions research, but also to expose K-12, undergraduate, and graduate students to a wide range of technological innovations.

该职业奖由材料研究部生物材料项目支持，旨在研究细胞外基质（ECM）的结构和机械性能。细胞外基质（extracellular matrix， ECM）是一种多蛋白网络，用于细胞与周围环境的沟通。这个教师早期职业发展（Career）项目的研究目标是：(1)从蛋白质（纳米级）到细胞（微观）水平表征ECM的结构和力学，(2)利用这些基本的理解来设计细胞培养平台，以研究功能和病理（癌症）环境中的血管化机制。鉴于该研究广泛的跨学科性质，该计划的主要教育目标是向学生（K-12，本科生和研究生）和教师（K-12计划）介绍材料和生物材料科学，生物力学，蛋白质物理学和细胞生物学的领域（以及使用的工具）。PI还将通过以下方式培养本科生和研究生，为将来在生物材料科学和/或工程领域的工作做好准备：(1)指导从大一到研究生阶段的学生进行研究；(2)将研究整合到她在康奈尔大学七个系教授的三门本科和研究生阶段的跨学科课程中。活细胞通过由邻近细胞和周围细胞外基质（ECM）纤维网络决定的化学和物理相互作用来感知和响应微环境。这个教师早期职业发展（Career）项目的主要目标是从纤维到细胞/组织水平研究ECM结构的两个主要组成部分（纤维连接蛋白和胶原蛋白）的结构和力学特性。该计划的优势在于跨学科的方法，结合了PI在(i) FRET（荧光共振能量转移）构象制图方面的专业知识，以及（ii）纳米和微观尺度上生物材料的机械表征。通过这些努力，PI将对ECM组成、构象和力学的调控机制产生基本的理解，这将使设计具有可控机械生物学特性的2D和3D细胞培养平台成为可能，用于研究生理和病理（癌症）环境中的血管形成机制。该项目不仅对生物材料科学有影响，而且对再生医学和组织工程也有影响，因为ECM在发育和癌症等疾病中起着重要作用；它不仅能促进细胞-基质相互作用研究的新方法，而且还能让K-12、本科生和研究生接触到广泛的技术创新，这一点也很重要。