A number of strategies exist to design molecular materials based on self-assembled peptides and their derivatives. [1] These include soft materials based on a variety of structural motifs including coiled-coils, [2,3] b-sheets, [4,5] b-hairpins, [6] and peptide amphiphiles. [7][8][9] In these systems, the peptide chains usually contain at least ten amino acids. It has been known for some time that using aromatic components in conjunction with peptides allows the use of much smaller peptides by taking advantage of p-stacking interactions. [10][11][12][13][14][15] One system that has been illustrated is that of N-fluorenylmethoxycarbonyl diphenylalanine (Fmoc-FF) which forms a hydrogel under physiological conditions. This example and other closely related aromatic short peptide derivatives are known to form fibrous hydrogels that have found applications in biological sensing [16] and cell culture. [13,17] Understanding of the supramolecular structures formed by these molecules will aid the rational design of new architectures tailored to the needs of specific biological and non-biological applications. However, to date a complete structure has not been proposed for any member of this class of self-assembly systems. Here we apply a number of spectroscopic techniques to Fmoc-FF and construct a model based on the data obtained comprising a new nanocylindrical molecular architecture based on p-p interlocked b-sheets. Transmission electron microscopy (TEM) and wide angle X-ray scattering (WAXS) was used to confirm the proposed model. Hydrogels of Fmoc-FF were prepared as described previously utilizing a sequential change in pH.[13] As shown in Figure 1a self-supporting gels were formed. The viscoelastic properties of the gels were assessed using oscillatory rheology. Figure 1b shows the mechanical spectrum obtained at room temperature for a Fmoc-FF (20 mmol L -1 ) gel. The storage modulus (G') is found to be approximately an order of magnitude larger than the loss modulus (G''), indicative of an elastic rather than viscous material. Both G' and G'' were found to be essentially independent of frequency over four decades (Fig. 1b). Such rheological behavior is characteristic of solid like gel materials. Light microscopy ( Fig. 1c) revealed a network of fine fibers with microscopic widths. Cryo Scanning Electron Microscopy (cryoSEM) revealed a dense network of flat ribbons with dimensions in the order of tens of nanometers (Fig. 1d). Circular dichroism (CD) was used to investigate the backbone orientation of the dipeptide within the hydrogel. CD analysis of peptide-based supramolecular materials is prone to artifacts. Usually only a narrow concentration range, where the hydrogel forms, can be used reliably to present a detectable CD signal, while showing no or little light scattering ef-

A number of short peptide amphiphiles consisting of dipeptides linked to fluorenylmethoxycarbonyl spontaneously form fibrous hydrogels under physiological conditions (see figure). The structural and physical properties of these gels are dictated by the amino acid sequence of the peptide building blocks, and the gels support the three‐dimensional cell culture of chondrocytes.

This tutorial review looks at the design rules that allow peptides to be exploited as building blocks for the assembly of nanomaterials. These design rules are either derived by copying nature (alpha-helix, beta-sheet) or may exploit entirely new designs based on peptide derivatives (peptide amphiphiles, pi-stacking systems). We will examine the features that can be introduced to allow self-assembly to be controlled and directed by application of an externally applied stimulus, such as pH, light or enzyme action. Lastly the applications of designed self-assembly peptide systems in biotechnology (3D cell culture, biosensing) and technology (nanoelectronics, templating) will be examined.

Peptides that self-assemble into nanostructures are of tremendous interest for biological, medical, photonic and nanotechnological applications. The enormous sequence space that is available from 20 amino acids probably harbours many interesting candidates, but it is currently not possible to predict supramolecular behaviour from sequence alone. Here, we demonstrate computational tools to screen for the aqueous self-assembly propensity in all of the 8,000 possible tripeptides and evaluate these by comparison with known examples. We applied filters to select for candidates that simultaneously optimize the apparently contradicting requirements of aggregation propensity and hydrophilicity, which resulted in a set of design rules for self-assembling sequences. A number of peptides were subsequently synthesized and characterized, including the first reported tripeptides that are able to form a hydrogel at neutral pH. These tools, which enable the peptide sequence space to be searched for supramolecular properties, enable minimalistic peptide nanotechnology to deliver on its promise.