NANOCAGE · The Development of Protein Cage-Based Inorganic Nano-Materials (resubmission)

Inorganic nanomaterials have attracted extensive attention as a result of their potential for a multitude of applications including those related to electronics and catalysis, and as part of sensors in medical diagnosis. Previously, we have described a new technique to generate gold nanoparticles inside the cavity of a ferritin cage protein by first forming a small nanocluster and using it as a seed for particle formation. Unlike previous techniques, this method does not require modification of the protein (e. g. engineering cysteine residues inside the cavity) and therefore has the potential to be used with any nanocage protein. This cage protein universality is a powerful aspect of our technology as the use of various cage proteins could provide synthetic vessels of different sizes and shapes, resulting in nanoparticles with different, and rationally defined, morphologies. Our method provides a second advantage in that the initial nanocluster could be used to seed other metals, resulting in protein-encapsulated, core-shell, dual-metal, nanoparticles. (These two advantages are exploited in Objective 1). Third, our method, by providing presumed universal flexible access to protein cages with different symmetries, sizes, and “handle” attachment sites, could provide, using the power and precision of molecular biology and advances in protein engineering, the opportunity to control the supra-assembly of the nanoparticles, and thus bridge the nano- and micro-scale through a “bottom-up” approach. (This third advantage is exploited in Objective 2) This extremely multi-disciplinary proposal, which marries molecular biology, protein engineering, and nanomaterials, aims to explore and expand upon the flexibility and advantages of our previous work by focusing on these three advantages to generate new hybrid materials.