The mammalian olfactory system provides great inspiration for the design of intelligent sensors. To this end, we have developed a bioinspired phage nanostructure-based color sensor array and a smartphone-based sensing network system. Using a M13 bacteriophage (phage) as a basic building block, we created structural color matrices that are composed of liquid-crystalline bundled nanofibers from self-assembled phages. The phages were engineered to express cross-responsive receptors on their major coat protein (pVIII), leading to rapid, detectable color changes upon exposure to various target chemicals, resulting in chemical- and concentration-dependent color fingerprints. Using these sensors, we have successfully detected 5-90% relative humidity with 0.2% sensitivity. In addition, after modification with aromatic receptors, we were able to distinguish between various structurally similar toxic chemicals including benzene, toluene, xylene, and aniline. Furthermore, we have developed a method of interpreting and disseminating results from these sensors using smartphones to establish a wireless system. Our phage-based sensor system has the potential to be very useful in improving national security and monitoring the environment and human health.

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Supporting Table Table S1. Crystallographic properties, crystallization conditions, and data collection and model refinement statistics for peptide 1. S2 Materials and Methods General information. S3 Synthesis of peptide 1. S3 Crystallization procedure for peptide 1. S5 X-ray crystallographic data collection, data processing, and structure determination for peptide 1. S6 Preparation of Aβ 40 and Aβ 42 oligomers S7 SDS-PAGE and silver staining. S8 Replica exchange molecular dynamics (REMD). S9 References and Notes S10

Oligomers of the β-amyloid peptide, Aβ, play a central role in the pathogenesis and progression of Alzheimer’s disease. Trimers and higher-order oligomers composed of trimers are thought to be the most neurotoxic Aβ oligomers. To gain insights into the structure and assembly of Aβ oligomers, our laboratory has previously designed and synthesized macrocyclic peptides derived from Aβ17–23 and Aβ30–36 that fold to form β-hairpins and assemble to form trimers. In this study, we found that mutating Phe20 to cyclohexylalanine (Cha) in macrocyclic Aβ-derived peptides promotes crystallization of an Aβ-derived peptide containing the Aβ24–29 loop (peptide 3 F20Cha ) and permits elucidation of its structure and assembly by X-ray crystallography. X-ray crystallography shows that peptide 3 F20Cha forms a hexamer. X-ray crystallography and SDS-PAGE further show that trimer 4 F20Cha , a covalently stabilized trimer derived from peptide 3 F20Cha , forms a dodecamer. Size exclusion chromatography shows that trimer 4 F20Cha forms higher-order assemblies in solution. Trimer 4 F20Cha exhibits cytotoxicity against the neuroblastoma cell line SH-SY5Y. These studies demonstrate the use of the F20Cha mutation to further stabilize oligomers of Aβ-derived peptides that contain more of the native sequence and thus better mimic the oligomers formed by full-length Aβ.

This paper describes the synthesis, solution-phase biophysical studies, and X-ray crystallographic structures of hexamers formed by macrocyclic β-hairpin peptides derived from the central and C-terminal regions of Aβ, which bear “tails” derived from the N-terminus of Aβ. Soluble oligomers of the β-amyloid peptide, Aβ, are thought to be the synaptotoxic species responsible for neurodegeneration in Alzheimer’s disease. Over the last 20 years, evidence has accumulated that implicates the N-terminus of Aβ as a region that may initiate the formation of damaging oligomeric species. We previously studied, in our laboratory, macrocyclic β-hairpin peptides derived from Aβ16–22 and Aβ30–36, capable of forming hexamers that can be observed by X-ray crystallography and SDS-PAGE. To better mimic oligomers of full length Aβ, we use an orthogonal protecting group strategy during the synthesis to append residues from Aβ1–14 to the parent macrocyclic β-hairpin peptide 1, which comprises Aβ16–22 and Aβ30–36. The N-terminally extended peptides N+1, N+2, N+4, N+6, N+8, N+10, N+12, and N+14 assemble to form dimers, trimers, and hexamers in solution-phase studies. X-ray crystallography reveals that peptide N+1 assembles to form a hexamer that is composed of dimers and trimers. These observations are consistent with a model in which the assembly of Aβ oligomers is driven by hydrogen bonding and hydrophobic packing of the residues from the central and C-terminal regions, with the N-terminus of Aβ accommodated by the oligomers as an unstructured tail.