“...we found that in the presence of gold-binding protein in solution, flat gold particles formed instead of the spherical ones like those Michael Faraday had formed 200 years earlier in England.”

The paper describes a new research philosophy that will potentially make a significant impact on the future of materials science, in particular, and engineering, in general. In this new direction, genetically engineered polypeptides and proteins are utilized as agents for materials formation, assembly, and immobilization. We call this new approach "molecular biomimetics," i.e., mimicking biological molecules that control material structures and functions, starting from the molecular scale, for purposes of practical applications. Researchers from various fields probably recognized that the inorganic-binding polypeptides we discuss in our paper are a new class of molecules that are genetically engineered and have great potential for materials sciences, engineering, and medical fields.

We describe, in this review paper, molecular biology protocols in the selection and isolation of 7-15 amino acid long polypeptides with a selective affinity to bind to practical inorganic materials that have functional properties (such as electronic, photonic, and magnetic), their molecular characterization through experimental and theoretical modeling tools, and we give practical examples of their applications in current and future technologies. We describe methods for selection, post-selection engineering, and theoretical bases for potential applications that could be useful for researchers both in materials sciences and engineering, including chemistry and physics, and medical fields (cancer probing, proteomics, biomaterials, therapeutic devices, and tissue engineering).

In organisms, proteins are the major molecular building blocks; they are not only the essential constituents of the soft and the hard tissues, such as muscle and bone, but they are also the functional units that carry information among all parts of the body that make an organism a viable entity, able to stand and function. Proteins do this via specific interactions that lead to molecular recognition and self/co-assembly into hierarchical structures. Acquiring lessons from biology, physical scientists and engineers could develop novel protocols where proteins could be major players in fabricating materials and making them functional through their specific interactions with the metals, ceramics, polymers, and semiconductors that we use every day.

During the late the 1980s and throughout the 1990s we were involved in establishing structure-property correlations in biological hard tissues, such as mollusk shells, bacterial nanoparticles, spicules, spines, dental tissues, and various bones. As materials scientists, we were excited to recognize the highly ordered, uniform, and hierarchical structures of these biological tissues, and contemplated mimicking them in synthetic materials for practical applications. In particular, we were interested in the mechanical (and later on, in the magnetic and optical) properties of these biological materials. We knew that proteins, as well as other macromolecules, would be involved in the fabrication of the complex architectures with hierarchical organization which these biological hard tissues have, that result in their possessing highly desirable engineering properties. Since all hard tissues contained proteins, we wanted to regenerate these tissues using the proteins extracted from them, to find out whether we could achieve the same control in doing so in synthetic materials engineering applications. However, isolation, purification, and the use of these proteins in the regeneration of their bioinorganics had been an enormous task, simply because biological materials contain not one but many proteins that are temporally and spatially involved in tissue formation. Because of these difficulties, therefore, no one has been able to regenerate a biological hard tissue so far.

We then searched for possible "off-the-shelf" proteins with an ability to bind to inorganics. There was none. Collaborating with Professor Stanley Brown of the University of Copenhagen, who had by 1996 adapted/developed a cell-surface display technology, and who had started to isolate polypeptides for iron oxide, a search was initiated for gold-binding proteins. While iron can have various oxide forms on its surface which could cause a problem in the binding specificity of selected polypeptides, we were, at this initial stage, interested in gold primarily because it is a noble metal, stable in water, has well-characterized surfaces, and is important technologically—such as a conductor in microchips. With Professor Brown, during his extended visit to the University of Washington, we searched for polypeptides that not only bound to gold but also affected its formation and shape. Specifically, we found that in the presence of gold-binding protein in solution, flat gold particles formed instead of the spherical ones like those Michael Faraday had formed 200 years earlier in England. Ours was the first demonstration of genetically engineered polypeptide controlled materials formation, specifically material morphogenesis. In 1997 we organized a workshop entitled "The Nature of Protein-Inorganic Interfaces," at Friday Harbor Marine Labs in San Juan Island, WA, which was attended by materials scientists and biologists. Discussions focused on synthetic evolution processes in the selection and isolation of inorganic-binding polypeptides. This gathering helped culminate in what we now call the "molecular biomimetics" field. The subsequent years have provided time to adapt and develop new and improved molecular biology protocols for the process of using engineering polypeptides for practical applications. Our recent collaborative projects, carried out through close and polydisciplinary collaborations among molecular biologists, materials scientists, and engineers, is focusing not only on selecting, but rigorously engineering these polypeptides to tailor molecular structures, and nano- and micro-scale architectures, towards controlling their binding and assembly characteristics as new bio-based building blocks in hybrid engineered materials and also in recently explored medical applications as biosynthesizers, molecular erectors, delivery systems, and templates. In this and subsequent publications, we are pursuing our goals of creating the fundamental basis for novel materials, entities, and systems for practical technologies.