RUI: Nanomagnetism of FeOOH-phases Grown within Native and Variant Apoferritin Nanotemplates.

RUI：在天然和变体脱铁铁蛋白纳米模板中生长的 FeOOH 相的纳米磁性。

• 批准号: 0604049
• 负责人: Georgia Papaefthymiou
• 金额: $ 19.2万
• 依托单位: Villanova University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0604049&HistoricalAwards=false
• 关键词: RUI; Nanomagnetism; FeOOH; phases; Grown

Non-technical AbstractBiomineralization of inorganic compounds on organic substrates in biology is at the center of nanoscience and nanotechnology that seek to emulate nature in the production of new materials at the nanoscale for bio-medical applications. Ferritin, the iron storage protein in living systems, including humans, is a natural laboratory for the production of iron hydroxide nano-phases sequestered within a robust protein shell with interior diameter of 7 nano-meters. This evolutionary iron management process provides for (a) detoxification of the cell from harmful radicals produced by free iron and (b) a readily available pool of iron to be used in the production of hemoglobin, myoglobin, the cytochromes and other iron-containing proteins necessary for respiration and metabolic processes. In this study iron biomineralization will be studied in native and mutant ferritins under different oxidation conditions. The magnetic, electronic and structural properties of the resulting biomineral nanophases will be characterized at different stages of iron nucleation and accumulation within the protein shell. It is expected that the results of this investigation will impact on our understanding and management of iron-related diseases and on the use of the ferritin protein shell as an organic template for the production of novel, biocompatible, magnetic nanophases for various biomedical applications, such as, Magnetic Resonance Image (MRI) enhancement and targeted drug delivery. A number of undergraduate students will participate in this project contributing to integration of research and education in nanoscience at Villanova University.Technical AbstractThe process of biomineralization of inorganic compounds on organic substrates in biology is at the center of nanoscience and nanotechnology that seek to emulate nature in the production of new materials at the nanoscale. Ferritin holds a special place in this field. Its ferroxidase and detoxification activity in the cell, its role in iron overloading diseases and DNA protection, the observed macroscopic quantum tunneling of magnetization (MQT), and the use of apoferritin as a molecular template for the synthesis of novel magnetic nanoparticles make this protein a supramolecular system of truly multidisciplinary interest in nanoscale science. In this investigation the magnetic properties of the 7-nm ferritin biomineral core obtained under different iron oxidation and deposition conditions in (a) native Horse Spleen apoFerritin (HoSF), (b) recombinant Human H-Chain apoFerritin (HuHF) and (c) mutant HuHF will be studied. Superconducting Quantum Interference Device (SQUID) magnetometry, Mossbauer spectroscopy and Ferromagnetic Resonance (FMR) measurements will be combined affording three different characteristic-measuring-time-windows to probe dynamic spin-relaxation processes at the nanoscale. Specifically, the superparamagnetism of fractionated, monodispersed HoSF obtained through analytical ultra-centrifugation will be investigated in order to elucidate the evolution of magnetic behavior as a function of size. Phases obtained using oxygen or hydrogen peroxide as the oxidant will be compared, as well as, phases grown within mutant HuHF where, by site directed mutagenesis the Glu64 and Glu67 residues at the C-nucleation site of HuHF apoferritin will be replaced by Ala, which lacks carboxylic groups. The proposed studies will advance fundamental knowledge in the behavior of anti-ferromagnetic nano-lattices; elucidate processes occurring at the organic/inorganic interface and; explore the stabilization of new iron nanophases within the ferritin cavity. Elucidation of iron biomineralization processes will impact on our better understanding and management of iron related diseases and the production of biocompatible magnetic nanophases with potential applications to biomedicine such as Magnetic Resonance Image (MRI) enhancement and targeted drug delivery. Furthermore, the data on monodispersed HoSF will elucidate MQT processes. A number of undergraduate students will participate in this project which will enhance the infrastructure for research/education at Villanova U. As this investigation is collaborative, it will promote collaborative cross-disciplinary research in nanoscience between an undergraduate institution (Villanova University) and a larger Research University (University of New Hampshire), and a National Laboratory, (National Institute of Standards and Technology, NIST-Colorado).

摘要生物学中有机基质上无机化合物的生物矿化是纳米科学和纳米技术的核心，纳米科学和纳米技术寻求在纳米尺度上模仿自然生产用于生物医学应用的新材料。铁蛋白是包括人类在内的生命系统中的铁储存蛋白，是生产氢氧化铁纳米相的天然实验室，这些纳米相被隔离在内直径为7纳米的坚固蛋白质壳中。这种进化的铁管理过程提供了(a)细胞从游离铁产生的有害自由基中解毒，(b)一个现成的铁池，用于生产血红蛋白、肌红蛋白、细胞色素和其他呼吸和代谢过程所必需的含铁蛋白质。本研究将研究不同氧化条件下天然铁蛋白和突变铁蛋白的铁生物矿化作用。所得到的生物矿物纳米相的磁性、电子和结构特性将在铁成核和蛋白质壳内积累的不同阶段进行表征。预计这项研究的结果将影响我们对铁相关疾病的理解和管理，并将铁蛋白外壳作为有机模板用于生产新的、生物相容性的磁性纳米相，用于各种生物医学应用，如磁共振成像（MRI）增强和靶向药物输送。一些本科生将参与这个项目，为维拉诺瓦大学纳米科学的研究和教育的整合做出贡献。在生物学中，无机化合物在有机基质上的生物矿化过程是纳米科学和纳米技术的核心，纳米科学和纳米技术寻求在纳米尺度上模仿自然生产新材料。铁蛋白在这个领域占有特殊的地位。它在细胞中的铁氧化酶和解毒活性，它在铁超载疾病和DNA保护中的作用，观察到的宏观量子隧道磁化（MQT），以及使用载铁蛋白作为合成新型磁性纳米颗粒的分子模板，使这种蛋白质成为纳米尺度科学中真正具有多学科兴趣的超分子系统。本研究将研究(a)天然马脾载铁蛋白（HoSF）， (b)重组人h链载铁蛋白（HuHF）和(c)突变体HuHF中不同铁氧化和沉积条件下获得的7纳米铁蛋白生物矿物核的磁性能。超导量子干涉器件（SQUID）磁强计、穆斯堡尔光谱学和铁磁共振（FMR）测量将结合起来，提供三种不同的特征测量时间窗，以探测纳米尺度上的动态自旋弛豫过程。具体来说，通过分析超离心获得的分馏单分散HoSF的超顺磁性将被研究，以阐明磁性行为随尺寸的变化。将比较用氧或过氧化氢作为氧化剂获得的相，以及突变体HuHF中生长的相，其中，通过位点定向诱变，HuHF载铁蛋白c核位点的Glu64和Glu67残基将被缺乏羧基的Ala取代。提出的研究将推进反铁磁纳米晶格行为的基础知识；阐明发生在有机/无机界面的过程；探索铁蛋白腔内新铁纳米相的稳定性。铁生物矿化过程的阐明将影响我们更好地理解和管理铁相关疾病，以及生物相容性磁性纳米相的生产，具有潜在的应用于生物医学，如磁共振成像（MRI）增强和靶向药物递送。此外，单分散HoSF上的数据将阐明MQT过程。许多本科生将参与这个项目，这将增强维拉诺瓦大学的研究/教育基础设施。由于这项调查是合作的，它将促进本科机构（维拉诺瓦大学）和一个较大的研究型大学（新罕布什尔大学）以及一个国家实验室（国家标准与技术研究所，NIST-Colorado）之间在纳米科学方面的跨学科合作研究。