CAREER: Solid State NMR Characterization Of Molecular Structure And Self-Assembly Of Protein Nanofiber Matrices

职业：分子结构的固态核磁共振表征和蛋白质纳米纤维基质的自组装

• 批准号: 1055215
• 负责人: Anant Paravastu
• 金额: $ 40.5万
• 依托单位: Florida State University
• 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: 2011-01-15 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1055215&HistoricalAwards=false
• 关键词: CAREER; Solid; State; NMR; Characterization

ID: MPS/DMR/BMAT(7623) 1055215 PI: Paravastu, Anant ORG: Florida State UniversityTitle: CAREER: Solid State NMR Characterization of Molecular Structure and Self-Assembly of Protein Nanofiber MatricesINTELLECTUAL MERIT: The goal of this proposal is to measure secondary structure and inter-atomic distances within designer protein nanofiber matrices with sufficient accuracy using solid state NMR methods to establish definitive structural models. Subjects of study will be the peptides RADA16-I (Zhang et al.), MAX1 and MAX8 (Schneider et al.), and SAF-p1/SAF-p2a (Woolfson et al.), each with a specifically designed self-assembly pattern. The PI will evaluate molecular level details of nanofiber self-assembly and self-healing processes. The motivation for this work is to establish a molecular level basis for engineering structure and properties of self-assembled protein matrices. Among potentially desired properties are those possessed by naturally derived protein matrices, such as strength and toughness, broad diversity of chemical and physical functionalities, and ability to self-assemble and self-heal in response to stimuli. Specifically, the following tasks will be completed during the grant period: (1) Measure secondary structure and inter-atomic distances with sufficient accuracy to formulate a structural model for RADA16-I nanofibers. (2) Formulate structural models for MAX1 and MAX8 nanofiber scaffolds. (3) Characterize the surface interactions between alpha-helices in SAF-p1/SAF-p2a nanofibers. (4) Test a recently proposed mechanism of self-healing of RADA16-I nanofibers. (5) Track self-assembled peptide particle sizes for short self-assembly times. (6) Quantify the nanofiber formation kinetics by varying soluble species concentrations. In the long term, this work will establish detailed structural understanding necessary to more effectively use self-assembling peptides as building blocks for scaffolds that support tissue growth and cell differentiation, hydrogels for drug delivery, and molecular templates for organization of other nanostructures (e.g., nanotubes and nanowires). On the nano-scale, material properties would ideally be determined by modular elements and simple design rules, so that a designed protein matrix could contain different domains optimized for specific mechanical properties, interactions that mediate cellular signaling, chemical functionality, or electrical conductivity.BROADER IMPACTS: The broader impact of this work lies in establishing a biomimetic bottom-up approach to nanomaterial construction with applications in regenerative medicine and nanotechnology. Biological nanotechnology will benefit from systematic methods to integrate structural protein domains with chemically and biologically active molecules and further interface with biological and non-biological components at multiple lengths scales. Principles established by this work will lead to design of versatile nanomaterials with a level of sophistication that rivals natural systems and surpasses present lithography-based micropatterning technologies. Furthermore, since proteins self-assemble primarily through noncovalent interactions, guided protein self-assembly is a promising route to producing self-healing and environment-responsive materials. This work includes several avenues for positive broader societal impacts. The FAMU-FSU College of Engineering is home to a diverse student body where 42% of the undergraduate student population belongs to traditionally under-represented groups; these students will be encouraged to participate in undergraduate research and pursue graduate study. The current and future research findings will be integrated into new coursework for a wide range of student age groups. Mentoring in research activities of Ph.D. candidates, undergraduates, and schoolteachers will provide a stimulating environment for learning and discovery. Outreach activities will stimulate enthusiasm for science and technology among children and families and middle through high school students. The target audience includes students from underrepresented groups in a nearby rural county.

ID：MPS/DMR/BMAT（7623）1055215 PI：Paravastu，Anant ORG：佛罗里达州立大学职业：固态NMR表征蛋白质纳米纤维基质的分子结构和自组装智力优势：该提案的目标是使用固态NMR方法以足够的精度测量设计蛋白质纳米纤维基质内的二级结构和原子间距离，以建立确定的结构模型。 研究的对象是肽RADA 16-I（Zhang等人），MAX 1和MAX 8（Schneider等人），和SAF-p1/SAF-p2 a（Woolfson等），每一个都有专门设计的自组装模式。 PI将评价生物相容性自组装和自修复过程的分子水平细节。 这项工作的动机是建立一个分子水平的基础，工程结构和自组装蛋白质基质的性质。 在潜在的期望性质中，有天然来源的蛋白质基质所具有的那些性质，例如强度和韧性、化学和物理功能的广泛多样性以及响应于刺激而自组装和自愈的能力。 具体而言，在资助期间将完成以下任务：（1）以足够的精度测量二级结构和原子间距离，以制定RADA 16-I纳米纤维的结构模型。 (2)建立了MAX 1和MAX 8骨水泥支架的结构模型。 (3)表征SAF-p1/SAF-p2 a纳米纤维中α-螺旋之间的表面相互作用。 (4)测试最近提出的RADA 16-I纳米纤维自愈机制。 (5)跟踪自组装肽颗粒尺寸，缩短自组装时间。 (6)通过改变可溶性物质浓度来量化凝胶形成动力学。 从长远来看，这项工作将建立必要的详细结构理解，以更有效地使用自组装肽作为支持组织生长和细胞分化的支架的构建块，用于药物递送的水凝胶，以及用于组织其他纳米结构的分子模板（例如，纳米管和纳米线）。 在纳米尺度上，材料特性理想地由模块化元件和简单的设计规则决定，这样设计的蛋白质基质可以包含针对特定机械特性、介导细胞信号传导的相互作用、化学功能或电导率进行优化的不同结构域。这项工作的更广泛的影响在于建立一个仿生自下而上的方法，纳米材料的建设与再生医学和纳米技术的应用。生物纳米技术将受益于系统的方法，以整合结构蛋白质结构域与化学和生物活性分子，并进一步与生物和非生物组分在多个长度尺度的接口。 这项工作建立的原则将导致设计多功能纳米材料的复杂程度，竞争对手的自然系统和超越目前的光刻为基础的微图案技术。 此外，由于蛋白质主要通过非共价相互作用进行自组装，因此引导蛋白质自组装是生产自修复和环境响应材料的有希望的途径。 这项工作包括产生更广泛的积极社会影响的若干途径。 FAMU-FSU工程学院是一个多元化的学生团体，其中42%的本科生属于传统上代表性不足的群体;这些学生将被鼓励参加本科研究并攻读研究生课程。 目前和未来的研究结果将被整合到广泛的学生年龄组的新课程。 指导博士研究活动。考生、本科生和教师将提供一个激励学习和发现的环境。 推广活动将激发儿童、家庭和中学生对科学和技术的热情。 目标受众包括来自附近农村县代表性不足群体的学生。