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 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.
The 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).
