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

非技术摘要无机化合物在生物有机基质上的生物矿化是纳米科学和纳米技术的核心，它们试图在纳米级生产用于生物医学应用的新材料时模仿自然。铁蛋白是包括人类在内的生命系统中的铁储存蛋白质，是生产氢氧化铁纳米相的天然实验室，氢氧化铁纳米相被隔离在一个内径为7纳米的坚固蛋白质壳中。这一进化的铁管理过程提供：(A)使细胞从游离铁产生的有害自由基中解毒；(B)提供现成的铁库，用于生产血红蛋白、肌红蛋白、细胞色素以及呼吸和代谢过程所需的其他含铁蛋白质。在这项研究中，铁的生物矿化作用将在不同的氧化条件下在天然铁蛋白和突变铁蛋白中进行研究。所得到的生物矿物纳米相的磁性、电子和结构性质将在蛋白质壳内铁成核和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，以及将铁蛋白蛋白外壳用作有机模板来生产用于各种生物医学应用的新型、生物兼容的磁性纳米相，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做出贡献。技术摘要在生物学中，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中心，这些纳米科学和技术寻求在纳米尺度上模仿自然生产新材料。铁蛋白在这一领域占有特殊的地位。它在细胞中的铁氧合酶和解毒活性，它在铁超载疾病和DNA保护中的作用，观察到的宏观磁化量子隧道(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，使该蛋白质成为纳米科学中真正多学科感兴趣的超分子系统。本研究将研究在不同铁氧化和沉积条件下获得的7 nm铁蛋白生物矿物核在(A)天然马脾载脂蛋白(HoSF)、(B)重组人H链载脂蛋白(HUHF)和(C)突变体HUHF中的磁性。超导量子干涉器件(SQUID)磁测量、穆斯堡尔谱和铁磁共振(FMR)测量将结合在一起，提供三个不同的特征测量时间窗口来探测纳米级的动态自旋弛豫过程。具体地说，将研究通过分析超离心法获得的分离的、单分散的HoSF的超顺磁性，以阐明磁行为随尺寸的变化。将比较使用氧或过氧化氢作为氧化剂获得的相，以及在突变体HUHF中生长的相，其中，通过定点突变，HUHF Apoferritin C-成核位置的Glu64和Glu67残基将被缺少羧基的Ala取代。拟议的研究将促进反铁磁纳米晶格行为的基础知识；阐明在有机/无机界面发生的过程；以及探索新的铁纳米相在铁蛋白空腔内的稳定。阐明铁的生物矿化过程将对我们更好地理解和管理铁相关疾病以及生产生物相容的磁性纳米相具有潜在的生物医学应用，如磁共振成像(MRI)增强和靶向给药将产生影响。此外，单分散HOSF的数据将阐明MQT过程。许多本科生将参与这个项目，该项目将加强维拉诺瓦大学研究/教育的基础设施，因为这项调查是合作的，它将促进一个本科机构(维拉诺瓦大学)和一个更大的研究型大学(新汉普郡大学)和一个国家实验室(国家标准与技术研究所，NIST-科罗拉多州)之间在纳米科学方面的跨学科合作研究。

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).