Most natural (or biological) materials are complex composites whose mechanical properties are often outstanding, considering the weak constituents from which they are assembled. These complex structures, which have risen from hundreds of million years of evolution, are inspiring Materials Scientists in the design of novel materials.Their defining characteristics, hierarchy, multifunctionality, and self-healing capability, are illustrated. Self-organization is also a fundamental feature of many biological materials and the manner by which the structures are assembled from the molecular level up. The basic building blocks are described, starting with the 20 amino acids and proceeding to polypeptides, polysaccharides, and polypeptides-saccharides. These, on their turn, compose the basic proteins, which are the primary constituents of 'soft tissues' and are also present in most biominerals. There are over 1000 proteins, and we describe only the principal ones, with emphasis on collagen, chitin, keratin, and elastin. The 'hard' phases are primarily strengthened by minerals, which nucleate and grow in a biomediated environment that determines the size, shape and distribution of individual crystals. The most important mineral phases are discussed: hydroxyapatite, silica, and aragonite.Using the classification of Wegst and Ashby, the principal mechanical characteristics and structures of biological ceramics, polymer composites, elastomers, and cellular materials are presented. Selected systems in each class are described with emphasis on the relationship between their structure and mechanical response. A fifth class is added to this: functional biological materials, which have a structure developed for a specific function: adhesion, optical properties, etc.An outgrowth of this effort is the search for bioinspired materials and structures. Traditional approaches focus on design methodologies of biological materials using conventional synthetic 0079-6425/$ -see front matter Ó

Spider silk is extraordinarily strong, mollusk shells and bone are tough, and porcupine quills and feathers resist buckling. How are these notable properties achieved? The building blocks of the materials listed above are primarily minerals and biopolymers, mostly in combination; the first weak in tension and the second weak in compression. The intricate and ingenious hierarchical structures are responsible for the outstanding performance of each material. Toughness is conferred by the presence of controlled interfacial features (friction, hydrogen bonds, chain straightening and stretching); buckling resistance can be achieved by filling a slender column with a lightweight foam. Here, we present and interpret selected examples of these and other biological materials. Structural bio-inspired materials design makes use of the biological structures by inserting synthetic materials and processes that augment the structures' capability while retaining their essential features. In this Review, we explain this idea through some unusual concepts.

RNA silencing processes are guided by small RNAs known as siRNAs and microRNAs (miRNAs) . They reside in ribonucleoprotein complexes, which guide the cleavage of complementary mRNAs or affect stability and translation of partial complementary mRNAs . Argonaute (Ago) proteins are at the heart of silencing effector complexes and bind the single-stranded siRNA and miRNA . Our biochemical analysis revealed that Ago2 is present in a pre-miRNA processing complex that is able to transfer the miRNA into a target-mRNA cleaving complex. To gain insight into the function and composition of RNA silencing complexes, we purified Ago1- and Ago2-containing complexes from human cells. Several known Ago1- and/or Ago2-associated proteins including Dicer were identified, but also two novel factors, the putative RNA helicase MOV10, and the RNA recognition motif (RRM)-containing protein TNRC6B/KIAA1093. The new proteins localize, similar to Ago proteins, to mRNA-degrading cytoplasmic P bodies, and they are functionally required to mediate miRNA-guided mRNA cleavage.

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microRNAs (miRNAs) regulate the expression of mRNAs in animals and plants through miRNA-containing ribonucleoprotein particles (RNPs). At the core of these miRNA silencing effector complexes are the Argonaute (AGO) proteins that bind miRNAs and mediate target mRNA recognition. We generated HEK293 cell lines stably expressing epitope-tagged human AGO proteins and other RNA silencing-related proteins and used these cells to purify miRNA-containing RNPs. Mass spectrometric analyses of the proteins associated with different AGO proteins revealed a common set of helicases and mRNA-binding proteins, among them the three trinucleotide repeat containing proteins 6 (TNRC6A,-B,-C). mRNA microarray analyses of these miRNAassociated RNPs revealed that AGO and TNRC6 proteins bind highly similar sets of transcripts enriched in binding sites for highly expressed endogenous miRNAs, indicating that the TNRC6 proteins are a component of the mRNA-targeting miRNA silencing complex. Together with the very similar proteomic composition of each AGO complex, this result suggests substantial functional redundancy within families of human AGO and TNRC6 proteins. Our results further demonstrate that we have developed an effective biochemical approach to identify physiologically relevant human miRNA targets.