Smart Nanomaterials Inspired by Biology: Dynamic Assembly of Error-Free Nanomaterials in Response to Multiple Chemical and Biological Stimuli YI LU* AND JUEWEN LIU Department of Chemistry and Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana—Champaign, Urbana, Illinois 61801 Received September 11, 2006 ABSTRACT Three-dimensional functional nanoscale assembly requires not only self-assembly of individual nanomaterials responsive to external stimuli, such as temperature, light, and concentrations, but also directed assembly of many different nanomaterials in one-pot responsive to multiple internal stimuli signaling the needs for such materials at a specific location and a particular time. The use of functional DNA (DNAzymes, aptamers, and aptazymes) to meet these challenges is reviewed. In addition, a biology-inspired proof- reading and error correction method is introduced to cope with errors in nanomaterials assembly. 1. Promises and Challenges in 3D Nanomaterials Assembly Assembly of nanoscale functional materials has long been a focus of research, because these materials may find promising applications such as in nanoelectronics, pho- tonics, computing, environmental monitoring, medical imaging, and diagnostics. An ideal nanoscale photonic assembly is shown in Figure 1A. Toward making such a dream into reality, remarkable advances in synthetic techniques have already resulted in a diverse range of high-quality individual nanomaterials, such as nanopar- ticles, nanotubes, and nanowires, 1 which can serve as building blocks for assembly of more complex nanostruc- tures such as that shown in Figure 1A. 2–5 Having these building blocks alone is not enough, just like having proteins, DNA, and carbohydrates alone is not enough to form a living and functional cell; dynamic control of the assembly and communication among these nanomaterials with high spatial and temporal resolution is required to make them into functional devices. Biomaterials constantly provide inspiration to materials scientists and engineers. Most materials in biology are made of protein or protein scaffolds with inorganic minerals. Close examination of how these materials are made defines a number of challenges in a rough order of increasing difficulty (Figure 1B). For example, tremendous progress has been made not only in self-assembly of nanomaterials but also in directed assembly in response to external physical stimuli, such as temperature, light, ionic strength, or material concentration. 6 However, bio- materials are assembled under constant and ambient conditions, in response instead to internal chemical or biological stimuli that signal the need for initiation, growth, and termination of specific biomaterials at a specific location and at a particular time. Usually, many different materials grow in the same system, and in many cases, these materials are made in response to sophisti- cated multiple internal stimuli, often with cooperativity. 7 Finally, biology has developed a set of mechanisms to cope with errors in protein synthesis, which assures accuracy in the downstream materials assembly. So then how does Nature achieve such an amazing feat? One way Nature accomplishes this is through genetic control (Figure 1C). In a biological system, such as a human body, many materials (teeth, bones, and soft tissues) are assembled at the same time. When the need for initiation of a particular material arises, related genes are turned on in response to corresponding stimuli to transcribe mRNA, which then translate into proteins to assemble biomaterials. Materials disassembly, such as release of iron in ferritin, can also be controlled in this way. Genetically controlled materials synthesis is “smart” in the sense that these materials are responsive to their chemical and biological environment and can, in turn, affect the environment. Furthermore, Nature makes defect- free proteins not because it does not make errors, but because it has developed elaborate systems of proof- reading and error correction. 8,9 Inspired by biology, stimuli-responsive peptide and protein-based synthetic materials assembly and disassembly have been re- ported. 10–12 Nucleic acids are another important class of biopoly- mers. Recently, developments in biology have generated novel functional nucleic acids with binding and catalytic activities, just like proteins. 13 While most gene expressions are regulated through proteins, RNAs have recently been shown to be capable of fulfilling a similar role, and these are now called riboswitches. 14 These discoveries have thus remarkably expanded our understanding of nucleic acids from pure genetic materials to functional biopolymers * To whom correspondence should be addressed. E-mail: yi-lu@uiuc.edu. Phone: 217-333-2619. Fax: 217-333-2685. Yi Lu received his B.S. degree from Beijing University, P. R. China, in 1986 and his Ph.D. degree from the University of California at Los Angeles in 1992, under the direction of Professor Joan Selverstone Valentine. After two years of postdoctoral research in Professor Harry B. Gray’s group at the California Institute of Technology, he joined the Department of Chemistry at the University of Illinois at Urbana—Champaign in 1994, where he is now a Professor of Chemistry and an Alumni Scholar. In addition to Department of Chemistry, he is also affiliated with Department of Biochemistry, Department of Materials Science and Engineering, and the Beckman Institute for Advanced Science and Technology. His research interests focus on the design and engineering of metalloproteins as biocatalysts, in vitro selection of functional DNA as biosensors, and directed assembly of nanomaterials. Juewen Liu was born in Changsha, China, in 1978. He received his B.S. degree from the University of Science and Technology in Hefei, China, in 2000 and his Ph.D. degree from the University of Illinois at Urbana—Champaign in 2005. Presently, he is working in Professor Yi Lu’s group in the University of Illinois as a postdoctoral research associate. He is interested in functional DNA assembled nanostructures. Acc. Chem. Res. 2007, 40, 315–323 10.1021/ar600053g CCC: $37.00  2007 American Chemical Society VOL. 40, NO. 5, 2007 / ACCOUNTS OF CHEMICAL RESEARCH 315 Published on Web 05/03/2007