With wisdom gained from long experience, Mother Nature has evolved mechanisms of simplicity and elegance to synthesize soft and hard tissues exhibiting remarkable functional properties. Nature achieves these feats of engineering by making use of molecular building blocks and by controlling material assembly in a hierarchical manner from the nano- to the macroscale. With a growing understanding of the processes involved came the realization that biological principles may have applications for solving problems in human-made systems. Traditionally, biomimeticists have focused on emulating or duplicating biosystems using mostly synthetic components and conventional approaches. By merging recent advances in molecular biology and genetics with state-of-the-art engineering and characterization from the physical sciences, our goal is to shift the biomimetic materials science paradigm from imitating Nature to designing and engineering natural materials to perform artificial functions. In this Center, we combine Nature's proven molecular tools with synthetic nanoscale constructs to make molecular biomimetics a full-fledged methodology. To this end, we have assembled a multidisciplinary team with expertise in diverse and synergistic areas ranging from molecular biology and chemistry to materials sciences and engineering.
A. GEPI as Molecular Synthesizers Materialization
Inorganic materials synthesized by biological organisms (though biomineralization) often posses unique morphological and structural properties and are ideal models in designing functional engineering materials. Using molecular biomimetics protocols, we biocombinatorially selected more than 50 hydroxyapatite binding peptides and used certain ones to control formation and morphogenesis of phosphate-based minerals, inorganic components of bone and dental tissues, for the purpose of using the developed protocols towards tissue repair and/or engineering. See, M. Gungormus, H. Fong, I. W. Kim, J. S. Evans, C. Tamerler, and M. Sarikaya, Regulation of in vitro Calcium Phosphate Mineralization by Combinatorially Selected Hydroxyapatite-Binding Peptides", Biomacromolecules, in print (2008). (PDF)
B. GEPI as Molecular Erectors
Alkaline Phosphatase (AP), as many natural proteins, favor a denatured state at solid interfaces. Here, 5rGBP1 is genetically fused to act as a molecular erector as well as an interfacing buffer-zone to orient and maintain the natured state of AP. Fig B shows discretely bound AP via 5rGBP1 while Fig E shows WT-AP agglomerating and unnatured on the gold surface.
C. GEPI as Molecular Assemblers
Simultaneous peptide-directed immobilization of optical active nanostructures and fluorophores on same on NSL substrate (5 mm bead mask): schematic (A), dark field image of NSL substrate (B, left top), QDots throught gold-binding peptide (l-AuBP2) to gold (B, right top), FITC through quartz-binding peptide (QBP1) to glass (B, left bottom), overlay fluorescent image (B, right bottom), control experiments: no peptide but streptavidin-Qdots and FITC present (shown in Fig. 4).
D. In Silico Design of Novel Inorganic Binding Peptides
The robust utility of genetically engineered peptides for inorganics (GEPI) in practical nanotechnology and medicine requires labor-intensive selection, using genetic tools, and characterization, via advanced microscopy and spectroscopy. Based on the experimental knowledge, a recently developed in-silico protocol provides means to design novel peptide sequences with enhanced binding affinity and multifunctionality. The new approach has a great potential of accelerating the utility of GEPI as synthesizers and assemblers of nanoinroganics with applications as molecular-probes in bio- and chemical-sensing, as -scaffolds in regenerative medicine, and as -platforms in nanobiophotonics.