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

无机化合物在生物学中的有机基质上的生物矿化是纳米科学和纳米技术的中心，纳米科学和纳米技术试图模仿自然界在纳米尺度上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径为7纳米的坚固蛋白质壳内。 这种进化的铁管理过程提供了（a）细胞对游离铁产生的有害自由基的解毒和（B）易于获得的铁库，用于生产血红蛋白、肌红蛋白、细胞色素和呼吸和代谢过程所必需的其他含铁蛋白质。 在这项研究中，铁的生物矿化将研究在天然和突变铁蛋白在不同的氧化条件下。 所得到的生物矿物纳米相的磁性，电子和结构特性的特征在于在不同阶段的铁成核和蛋白质壳内的积累。 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，以及使用铁蛋白蛋白壳作为有机模板，用于生产用于各种生物医学应用的新型生物相容性磁性纳米相，如磁共振成像（MRI）增强和靶向药物递送。 一些本科生将参加这个项目有助于在维拉诺瓦大学纳米科学的研究和教育的整合。技术摘要在生物学中的有机基板上的无机化合物的生物矿化过程是在纳米科学和纳米技术的中心，寻求模仿自然在纳米级的新材料的生产。 铁蛋白在这一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，观察到的宏观量子磁化隧道（MQT），以及使用脱铁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科学中真正多学科兴趣的超分子系统。在本研究中，将研究在不同铁氧化和沉积条件下在（a）天然马脾脱辅基铁蛋白（HoSF）、（B）重组人H链脱辅基铁蛋白（HuHF）和（c）突变HuHF中获得的7-nm铁蛋白生物矿物核心的磁性。超导量子干涉器件（SQUID）的磁力测量，穆斯堡尔谱和铁磁共振（FMR）测量将结合起来，提供三个不同的特征测量时间窗口，以探测纳米级的动态自旋弛豫过程。 具体而言，超顺磁性的分馏，单分散HoSF通过分析超离心得到的将进行研究，以阐明作为大小的函数的磁行为的演变。 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HuHF内生长的相，其中通过定点诱变，HuHF脱铁铁蛋白的C-成核位点处的Glu 64和Glu 67残基将被缺乏羧基的Ala取代。 拟议的研究将推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;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和生物相容性磁性纳米相的生产，其具有潜在的生物医学应用，如磁共振成像（MRI）增强和靶向药物递送。此外，单分散HoSF的数据将阐明MQT过程。 一些本科生将参加这个项目，这将加强在维拉诺瓦大学的研究/教育的基础设施。 由于这项调查是合作的，它将促进本科院校（维拉诺瓦大学）和一个更大的研究型大学（新罕布什尔州大学）和国家实验室（国家标准与技术研究所，NIST-科罗拉多州）之间的纳米科学的跨学科合作研究。

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).