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Yohei Yamamoto, Wey Yih Heah, [Kentaro Tashiro](https://orcid.org/0000-0001-7424-0830)

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[Functional oligo- and polypeptide assemblies for photochemical, optical and electronic applications](https://mdr.nims.go.jp/datasets/1e217c60-9a43-4c0f-b95c-1d84b701771a)

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Functional oligo- and polypeptide assemblies for photochemical, optical and electronic applicationsAs featured in:  Highlighting a review by Yohei Yamamoto and Wei Yih Heah from the University of Tsukuba and Kentaro Tashiro from National Institute for Materials Science (NIMS), Japan  Functional oligo- and polypeptide assemblies for photochemical, optical and electronic applications  Controlled self-assembly of peptides can arrange molecular functions on the side chains as we intend. In this review, an overview is provided of the precise synthesis of self-assembled peptide assemblies for photochemistry, optics and electronics applications. The image shows possible applications with environmentally friendly peptide-based biomaterials.  See Yohei Yamamoto, Kentaro Tashiro  et al .,  Mater .  Horiz ., 2024,  11 , 3203.MaterialsHorizonsrsc.li/materials-horizons COMMUNICATION  Kang-Nan Wang, Zhiqiang Liu, Xiaoqiang Yu, Bin Liu  et al .  Dual-targeted fluorescent probe for tracking polarity and phase transition processes during lipophagy ISSN 2051-6347Volume 11Number 1421 July 2024Pages 3191–3452rsc.li/materials-horizonsRegistered charity number: 207890This journal is © The Royal Society of Chemistry 2024 Mater. Horiz., 2024, 11, 3203–3212 |  3203Cite this: Mater. Horiz., 2024,11, 3203Functional oligo- and polypeptide assembliesfor photochemical, optical andelectronic applicationsYohei Yamamoto, *a Wey Yih Heah a and Kentaro Tashiro *bThe primary and secondary structures of peptides are useful as scaffolds to sequentially arrange func-tional groups of molecules. In this review, we review self-assembled functional peptides, wherebypeptides with appropriate amino acid sequences can assemble using functional groups on their sidechains. First, we apply our design strategies for the synthesis of peptide-based materials with sequencedside chains with polar moieties, organic dyes and metal complexes. The synthetic oligopeptides thusobtained exhibit inherent photoinduced charge separation and electrochemical redox activities, as wellas responses to bio-sequences. Next, catalytic and photocatalytic oxidation reduction reactions andhydrogen evolution reactions are shown by utilizing the peptides with separated functionalities on bothsides of b-sheets by hybridizing with electro- and photoactive graphene oxide and metal nanoparticles.Finally, the self-assembled natural proteins that form micrometre-scale spherical geometry and fibresare utilized for optical and electronic applications. The silk fibroin forms well-defined microspheres withsmooth surface morphology, leading to properties suitable for use in optical resonators, which cansense external humidity because of the hygroscopic nature of silk fibroin. Dragline silk fibres can act asoptical waveguides that can perform intermediate natural polymer-based optical logic operations. Thesefunctional peptides are utilizable for various applications in catalysis, optics and electronics.Wider impactPeptides are one of the main components in our body and have an essential role in life activities. In this focused review, we show the possible application ofpeptide assemblies in not only living organisms and biomedical materials but also for other purposes, such as electrochemical, catalytic, optical, and electricalapplications, by utilizing the potential self-organizing ability of peptides. For example, peptide b-sheets can arrange the functional units, such as positive/negative charges, electron donor/acceptor units, and metal nanoparticles, leading to efficient photoinduced charge separation and photocatalytic reactions.Furthermore, self-assembled peptide assemblies can be used as components of optical sensing and optical logic devices, as well as organic electronic devices.This review includes the fundamentals of peptide assembling structures and ways in which molecular functional groups assemble using peptide scaffolds.These insights will be valuable to find the potential of peptides and their assemblies for applications in various fields.1. IntroductionThe ability to put components in their appropriate positionsis crucial, not only to manufacturing machinery but also toengineering a wide range of materials.1 When these materialsare supposed to be prepared through assembling molecules, anattractive option of compounds for this attempt would bepeptides, as their intrinsic structural features allow control offunctionalities over one-, two- and three-dimensional (1D, 2Dand 3D) orientations.2,3 First, the primary structure of a singlepeptide chain is composed of a sequence of multiple monomerunits, amino acids (AAs), whose side residue can be used asthe scaffold to selectively construct a specific 1D sequence ofmultiple functionalities (Fig. 1). Second, each peptide canadopt a particular conformation, such as helix, strand andturn, which is dependent on its primary sequence, while singleor multiple peptide chains form 2D sheets (b-sheet) that arecomposed of multiple strands aligned in parallel or anti-parallel fashion (Fig. 1). By taking advantage of this secondarystructure-forming capability of peptides, specific 2D and 3Dorientations of their side residues and functionalities areprogrammable through the judicious choice of the primarya Institute of Pure and Applied Sciences, University of Tsukuba, 1-1-1, Tennodai,Tsukuba, Ibaraki 305-8573, Japan. E-mail: yamamoto@ims.tsukuba.ac.jpb Research Center for Macromolecules & Biomaterials, National Institute forMaterials Science, 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan.E-mail: Tashiro.kentaro@nims.go.jpReceived 29th February 2024,Accepted 14th May 2024DOI: 10.1039/d4mh00218krsc.li/materials-horizonsMaterialsHorizonsREVIEWOpen Access Article. Published on 24 June 2024. Downloaded on 7/16/2024 5:00:20 AM.  This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.View Article OnlineView Journal  | View Issuehttps://orcid.org/0000-0002-2166-3730https://orcid.org/0009-0004-7485-1497https://orcid.org/0000-0001-7424-0830http://crossmark.crossref.org/dialog/?doi=10.1039/d4mh00218k&domain=pdf&date_stamp=2024-05-28https://rsc.li/materials-horizonshttp://creativecommons.org/licenses/by/3.0/http://creativecommons.org/licenses/by/3.0/https://doi.org/10.1039/d4mh00218khttps://pubs.rsc.org/en/journals/journal/MHhttps://pubs.rsc.org/en/journals/journal/MH?issueid=MH0110143204 |  Mater. Horiz., 2024, 11, 3203–3212 This journal is © The Royal Society of Chemistry 2024sequence of peptides (Fig. 1). When the length of a peptidechain becomes long enough to be regarded as a protein, anescalating number of possible 3D conformational outcomesallow its folding and self-assembly into non-natural micro-structures, creating unprecedented materials. This review sum-marizes the attempts of researchers, including us, for morethan a decade to design functional materials based on peptides.The reviewed studies mainly focus on two topics: (1) thedevelopment of novel synthetic strategies to reach unprece-dented structures of peptide-based materials that are difficultto achieve by conventional methods4,5 and (2) exploration ofthe physical/chemical properties of these materials to find outtheir applications.62. Strategies to design peptide-basedmaterials2.1. Covalent introduction of non-natural functionalities intopeptide side residuesFor the preparation of a peptide sequence with multiple non-natural functionalities that are covalently linked to side residues,two different synthetic approaches can be considered. The firstapproach is the sequentialization of amino acids, whose sideresidues have been modified in advance with one of the non-natural functionalities (Fig. 2a). This approach is theoreticallyuseful to produce targeted sequences in a defect-free form as allrequired functionalities can be quantitatively attached atexpected positions. It is also advantageous to introduce diversefunctionalities into single peptide chains, where even a singletype of amino acid side residue can be sufficiently used for site-specific covalent linkage of several different functionalities.This approach allowed us4,5,7,8 and other research groups9–12to obtain several peptide sequences with multiple organic,as well as metal complex, moieties.As a representative example, a terpyridine-appendedL-tyrosine derivative was designed for metalation with Pt(II),Rh(III), or Ru(II) ions to afford a series of metalated amino-acidmonomers.4 These monomers were sequentially coupled usingthe solid-phase peptide synthesis technique13,14 to producetyrosine oligomers with a specific heteronuclear multi-metallic sequence, such as Rh–Pt–Ru–Pt–Rh–Pt (Fig. 3a).As proved by our experimental results, this synthetic strategyeffectively works for the preparation of shorter peptides with 10or fewer functionalities in a single molecule. However, itsstraightforward application for the construction of longersequences containing monomers with a good number of varia-tions could be challenging due to the need to synthesise andcoupling an increasing number of monomer structures.Fig. 1 Schematic representations of primary and secondary structures ofpeptides. AA: Amino acid, Rn: Side chain at the n-th AA.Fig. 2 (a) Sequentialization of side-residue functionalized amino acidsand (b) post-modification of the side residues of a natural peptide toprepare peptide sequences with multiple non-natural functionalities thatare covalently linked to the side residues. Red arrows in schemes corre-spond to the steps of side-residue functionalization.Fig. 3 Molecular structures of side-residue functionalized peptides bear-ing (a) Rh–Pt–Ru–Pt–Rh–Pt and (b) Sm–Tb–Eu metal seaueces.Review Materials HorizonsOpen Access Article. Published on 24 June 2024. Downloaded on 7/16/2024 5:00:20 AM.  This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.View Article Onlinehttp://creativecommons.org/licenses/by/3.0/http://creativecommons.org/licenses/by/3.0/https://doi.org/10.1039/d4mh00218kThis journal is © The Royal Society of Chemistry 2024 Mater. Horiz., 2024, 11, 3203–3212 |  3205The latter issue has been partly addressed by introducing amodular strategy, where shorter sequences prepared via solid-phase synthesis protocols were site-specifically linked insolution to produce longer linear or branched structures.5To avoid the randomization of constructed metal sequencesthrough undesired ligand–metal exchange or demetalla-tion,15,16 it is crucial to choose the ligand structure judiciously.Because of the sufficiently low level of ligand–metal exchangeactivity, multidentate ligands, such as terpyridine,4 phen-anthroline,17–19 and porphyrin,5 turned out to be useful choices.Later, another research group developed a cryptate-based ligandsystem that could bind and exchange labile lanthanoid ions firmlyby taking advantage of its capability to encapsulate metal ions(Fig. 3b).12 The metal complex sequences, similar to underlyingamino acid sequences, were found to strongly affect the self-assembly behaviour of these multi-metalated peptide species,where their gelation17 or amyloid-like fibril formation7 was pro-moted by the presence of particular sequences, while a hetero-trimetallic peptide sequence exhibited an anti-Hofmeister trend inits anion-dependent aggregation.20The second approach to introduce non-natural functional-ities into the peptide side residues is the post-modification ofthe side residues in natural peptide sequences (Fig. 2b). This iscurrently regarded as a practical approach to obtaining side-residue functionalized long peptides. This approach is usefulwhen research goals allow an imperfect conversion of the sideresidues into planned functionalities, as well as when it isdifficult to perform a site-specific modification of the residuesin a single peptide with several types of functionalities.21,22While some of the side-residue functionalized peptides thusprepared have been used in the same way as their non-assembled forms,23 most were successively subjected to self-assembly to afford b-sheet-like secondary structures, where thefunctionalities attached can spontaneously adopt specific 2Dand 3D orientations to serve particular roles.2.2. Charge-separated peptide b-sheets with natural aminoacids with charged side chainsPeptide b-sheet is an appropriate scaffold to arrange molecularfunctionality. Pioneering works on the self-assembly of thepeptides with molecular functionality have been carried outby several groups, and excellent reviews on the fundamentalsand applications of self-assembled peptide assemblies werepublished.24–31 In the present review, we introduce researchresults on arranging molecular functionality on the top andbottom sides of the b-sheet.Nakayama et al. prepared peptide b-sheets, where positively-and negatively charged side chains, were separated on the topand bottom sides of the b-sheets (Fig. 4a).8 The strategy for theformation of charge-separated peptide b-sheets is that, in the b-sheets, side chains of odd- and even-numbered amino acids arearranged on the opposite side of the b-sheet. According to the 9-fluorenyl methoxycarbonyl (Fmoc)-peptide synthetic protocol,1318 Fmoc-pentapeptides, including valine (V, neutral), lysine(K, positive charge at the even position, R2 and/or R4), andglutamic acid (E, negative charge at the odd position, R1, R3,and/or R5), are synthesized, and their self-assembling behaviorsin MeOH are investigated with the slow addition of Et2O vapour.By X-ray diffraction (XRD) and transmission electron microscopy(TEM) studies, Fmoc-pentapeptides with one E and K each wereobserved to form b-sheet structures in the solid state after evapora-tion of the solvent for the self-assembled structure. However, whenthe b-sheets were added to a glycine buffer (pH = 8.5), only selectedsequences maintained the b-sheet structure, as revealed by thephotoluminescence (PL) test using thioflavin (ThT) that selectivelyemits PL upon adsorption on the b-sheet. Especially, Fmoc-peptideswith charged side chains at the central position (R3) keep the b-sheetstructure with difficulty because of the charge repulsion of thecharges aligned in the center of the antiparallel b-sheet (for example,Fmoc-VVEKV, Fig. 4b right). Accordingly, the necessary strategy forobtaining the charge-separated peptide b-sheet is to separate thecharges in the neighboring b-strands to reduce the charge repulsion(for example, Fmoc-VVVKE, Fig. 4b left). In contrast, when two pairsof E and K are introduced in the Fmoc-pentapeptide, b-sheetstructure is only formed from Fmoc-EKVKE and Fmoc-KEVEK arein the solid state, and all the other sequences sparsely form ab-sheet because of strong charge repulsion.2.3. Photoinduced charge separation of peptide b-sheets fromneighbouring electron donor–acceptor pairsAs proposed by Zhang et al., complementary charged peptidestend to form the b-sheets (Fig. 5a left).32 In Zhang’s model,positively and negatively charged side chains (E and K) areFig. 4 (a) Schematic representations of parallel and antiparallel peptide b-sheets. (b) Schematic representations of charge-separated peptide b-sheets with stable (left) and unstable (right) charge distributions. Repro-duced from ref. 8 with permission from Wiley-VCH, Copyright (2014).Materials Horizons ReviewOpen Access Article. Published on 24 June 2024. Downloaded on 7/16/2024 5:00:20 AM.  This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.View Article Onlinehttp://creativecommons.org/licenses/by/3.0/http://creativecommons.org/licenses/by/3.0/https://doi.org/10.1039/d4mh00218k3206 |  Mater. Horiz., 2024, 11, 3203–3212 This journal is © The Royal Society of Chemistry 2024arranged on one side of the b-sheet, while hydrophobic sidechains (V) are assembled on the other side. The alternatelyarranged charges interact electrostatically with one another andcompensate for the charges, which stabilizes the b-sheet struc-ture. Inspired by this model, Nakayama et al. proposed b-sheetdesigns with photoinduced charge separation, where electron-donating tetraphenylporphyrin (TPP) and electron-acceptingnaphthalene diimide (NDI) were alternately anchored on oneside of the b-sheet (Fig. 5a and b).33 In Nakayama’s model,electron-donor and acceptor molecular moieties are arrangedon one side of the peptide b-sheet, instead of positive andnegative charges in the charge-complementary peptide b-sheet.For synthesis, amino acid dimers of TPP-anchored lysineand valine (Fmoc-KTTPV–OH) and NDI-anchored glutamic acid(Fmoc-ENDIV–OH) are synthesized, which are further connectedwith Fmoc-V to form a heptapeptide, VENDIVKTPPVENDIV. Theheptapeptide self-assembles in aprotic 30% trifluoroethanol(TFE)-CHCl3 with slow addition of nonsolvent vapors of iso-propyl ether (IPE). As confirmed by spectroscopy and X-raydiffraction, the heptapeptide forms a b-sheet structure. PLquenching studies indicate that photoinduced electron transferoccurs efficiently from TPP to NDI moieties in the pentapep-tide. Further studies on the self-assembling structure revealthat the TPP moieties form a J-type aggregate in neutralconditions (30% TFE-CHCl3, Fig. 5c left). In contrast, underprotic conditions (50% TFE-hexafluoroisopropanol (HFIP)),the heptapeptide sparsely forms b-sheet due to the electronicrepulsion between protonated TPPs. The b-sheet formationbegins rapidly when deprotonation of the TPP moieties iscompleted by the addition of IPE. In the b-sheet, the TPP andNDI moieties separately form H- and J-type aggregates, respec-tively (Fig. 5c right).Segregated stacks of electron donor (D) and acceptor (A)molecules are achieved by utilizing the self-assembly behaviourof the peptides. Sanders et al. reported that A–D–A dyads ofquarterthiophene (D) and oligopeptide with NDI (A) form 1Dnanofibers in an aqueous media.34 Due to the separation of Dand A in the fibrous assembly, photoinduced electron transferoccurs with a long-lived charge-separated state (Fig. 6). Exam-ples of such precise control of segregated stacks of D and A in ananostructure are reported for self-assembled nanotubes withcoaxial structure, where an electron-donating core layer islaminated by an electron-accepting shell.35–37 Meanwhile, byutilizing the characteristics of a self-assembling peptide b-sheet, thesegregated stack of electron donor and acceptor molecular moietieson the side chains can be achieved.2.4. Design strategy for helix-forming non-natural peptidesThe helix is a representative secondary structure of peptides,which features a chiral 1D shape. As nature mostly uses theL-form of amino acid enantiomers as a result of long-termbiotic/prebiotic evolution processes, helices found in naturepossess single helicity. While individual helices are typicallyobtained through the intramolecular folding of a single peptidechain, they may sometimes consist of multiple peptides boundtogether. The ability of a peptide to form a helical structure isstrongly governed by its primary structure, where several helix-forming amino acid sequences have been identified. Accord-ingly, the most straightforward design strategy for a helix isto adopt one such sequence as the main component of theFig. 5 (a) Schematic representations of complementarily charged pep-tides (left, Zhang’s model) and electron donor–acceptor peptides (right,D–A model). (b) Molecular structures of pentapeptide, VENDIVKTPPVENDIV(left), electron-donating TPP derivative (right top) and electron-acceptingNDI derivative (right bottom). (c) Schematic representations of the self-assembled structures of the heptapeptide by diffusion of IPE vapor into30% TFE-CHCl3 (left) and 50% TFE-HFIP solutions (right). Reproducedfrom ref. 33 with permission from Chemical Society of Japan, Copyright(2017).Fig. 6 Illustration of self-assembly and electron transfer of a donor–acceptor p-peptide hybrid. Reproduced from ref. 34 with permission fromAmerican Chemical Society, Copyright (2016).Review Materials HorizonsOpen Access Article. Published on 24 June 2024. Downloaded on 7/16/2024 5:00:20 AM.  This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.View Article Onlinehttp://creativecommons.org/licenses/by/3.0/http://creativecommons.org/licenses/by/3.0/https://doi.org/10.1039/d4mh00218kThis journal is © The Royal Society of Chemistry 2024 Mater. Horiz., 2024, 11, 3203–3212 |  3207targeted non-natural peptide chain.38 Intra-helix interactionsbetween side residue functionalities also contribute to promot-ing or inhibiting helix formation.39Co-polymerization of g-propargyl-L-glutamic acid N-carb-oxyanhydride and N-e-2-[2-(2-methoxyethoxy)ethoxy]acetyl-L-ly-sine N-carboxyanhydride has been reported to create water-soluble polypeptides that adopt a-helical conformations.40 Theacetylene terminal attached to the glutamate side residue wasused for the click reaction to introduce another functionalityinto the polypeptides. When parent polypeptides were modifiedwith a cell-binding short peptide, GRGDS (Gly–Arg–Gly–Asp–Ser),the resultant polypeptide could retain its helical content, promotingthe adhesion of Chinese hamster ovary cells. Although, generally,helix-forming peptides must have a longer chain length than thosefor the b-sheets, Gly–Pro–Pro tripeptide bearing pyridyl moieties atits C- and N-terminals has been found to form a helical conforma-tion upon coordination to the Ag(I) ion to afford a crystalline porousnetwork.41 Owing to the helical conformation of this tripeptide, thecrystal offers chiral nanochannels working for the chiroselectiveuptake of guest molecules.3. Peptide b-sheets as crosslinkers andscaffolds for assembling catalytic metalnanoparticles (MNPs) and graphene oxideIn this section, applications for self-assembled peptide b-sheetswith separated functionality on opposite sides are introduced.Function-separated peptide b-sheets are useful for assemblingdifferent components on the top and bottom sides of theb-sheet. The characteristics of the function-separated peptideb-sheets are utilized as dispersants of agglomerated metalnanoparticles (MNPs). They are further applicable for use asscaffolds in the assembly of MNPs and graphene oxide (GO) forphoto- and electro-catalytic activity.3.1. Cysteine-containing peptide b-sheet as a redispersant ofagglomerated MNPsThe strategy shown in Section 2.2 to prepare oligopeptideb-sheets with separated functionalities on the top and bottomsides of the b-sheet is useful for various applications. Forexample, a Fmoc-pentapeptide b-sheet with a positively chargedamino group, such as lysine, on one side and a metal-bindingthiol group, such as that of cysteine, on the other side of theb-sheet can redisperse agglomerated MNPs (M = Au, Cu, Ptand Pd, Fig. 7a).42 Surfactant-free Au nanoparticles (AuNPs)prepared by laser ablation technique are originally highlydispersed in water and organic solvents due to the negativecharge on the surface of the AuNPs.43–47 However, the AuNPsgradually agglomerate after 6 months of preparation. By addingthe b-sheet of Fmoc-VKVVC 1 in MeOH, the AuNPs areenwrapped by the b-sheet with the thiol group on one side,while the aminobutyl group of lysine on the other side of theb-sheet maintains the dispersion state of the b-sheets in water/MeOH mixed solvent. Finally, after 3 days of aging, agglo-merated AuNPs are redispersed on the surface of the b-sheetFig. 7 (a) Schematic representation of the redispersion of MNPs by an addition of Fmoc-VKVVC 1 (b-sheet) in MeOH. Photographs show as-prepared AuNPdispersion in water (left top), AuNP dispersion in water 6 months after preparation (right top) and that added by MeOH solution of the b-sheet of 1 aged for 3 days(right bottom). Yellow sphere, green arrow and purple sphere on the green arrow indicate AuNP, b-strand of 1 and thiol side chain, respectively. (b) Schematicrepresentation of the hierarchical assembly of PtNPs, 1, and GO to form the PtNP/1/GO complex. (c) TEM micrographs of the PtNP/1/GO complex. (d) Schematicrepresentations of the pathways of photogenerated hole and electron for dye degradation (left) and H2 evolution (left). Reproduced from ref. 42 (a) and 48 (b–d)with permission from Royal Society of Chemistry, Copyright (2015) and American Chemical Society, Copyright (2017).Materials Horizons ReviewOpen Access Article. Published on 24 June 2024. Downloaded on 7/16/2024 5:00:20 AM.  This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.View Article Onlinehttp://creativecommons.org/licenses/by/3.0/http://creativecommons.org/licenses/by/3.0/https://doi.org/10.1039/d4mh00218k3208 |  Mater. Horiz., 2024, 11, 3203–3212 This journal is © The Royal Society of Chemistry 2024with the colour of the solution turning from blue (agglomeratedAuNPs) to original pink (dispersed AuNPs). A similar effect isobserved for agglomerated CuNPs, PtNPs and PdNPs.3.2. PtNPs/cysteine-containing peptide b-sheet/grapheneoxide composite for oxygen reduction and hydrogen generationreactionsUsing a function-separated b-sheet of 1, metal nanoparticlescan be immobilized on a graphene oxide (GO) nanosheet. GOsheets have negatively charged carboxy and hydroxy groups,which readily interact with positively charged amino groups onone side of the b-sheet of 1. As a result, the b-sheet of 1 coversthe surface of the GO sheet when mixed. By adding a solution ofPtNPs to the b-sheet/GO composite, the PtNPs bind to the thiolgroup of the b-sheet to form a highly condensed PtNPs/1/GOternary complex (Fig. 7b and c).48 Upon photoirradiation, thesuspension of PtNPs/1/GO ternary composite displays remark-able photocatalytic activity: GO absorbs light, and thus, anexcited electron transfers to PtNP, resulting in the oxidation–reduction reaction (ORR). The generated holes in GO aretransferred to the dye added, Rhodamine B (RhB), whichdegraded it through the oxidation of RhB (Fig. 7d, left). WhenNa2S2O4 is added as a hole scavenger, the ternary complexdisplays a hydrogen evolution reaction (HER) upon white lightirradiation (Fig. 7d, right).Another type of peptide/PtNP complex shows electrocatalyticORR.49 The heptapeptide, AAKLVFF, forms a b-sheet which hasthe amino groups of the lysine side chain and a terminal of thepeptide with a positive in water; therefore, the PtNPs withnegative surface potential form a PtNP/b-sheet complex withit. The ORR activity of the PtNP/b-sheet complex is higher thanthe benchmark Pt/C electrocatalyst in terms of the onsetpotential and reaction kinetics. Furthermore, the complex dis-plays one order of magnitude higher ORR mass activity thanpreviously reported peptide-based ORR electrocatalysts, whichare derived from well-dispersed PtNPs on the b-sheet, where50% amine groups function as active sites for the catalyticreaction.4. Self-assembled microstructuresfrom natural proteins for opticaland electronic applicationsIn this section, we introduce self-assembled natural proteinsthat can perform optical and electronic functions, such asFig. 8 (a) Photograph of mulberry silkworm and a schematic representation of silk fibroin microsphere that expand or contract in response tosurrounding humidity. (b) SEM micrograph of the SF microsphere. Scale bar: 5 mm. (c) PL spectra of a single SF microsphere upon excitation with a cwlaser (lex = 450 nm). Each WGM peak is assigned as shown at the bottom. (d) Humidity-dependent PL spectra of a single SF microsphere upon excitationwith a cw laser (lex = 450 nm). (e) Plot of the wavelength of the resonant peak of TE26 upon increasing (filled circle) and decreasing (open circle) thesurrounding humidity. (f) Plot of the wavelength of the resonant peak of TE26 upon six cycles of hydration (red) and dehydration (blue) between 93 and25% RH. (g) A schematic representation of the quantitative measurements of the hydrolysis reaction based on the spectral shift of the resonance peaks.(h) Schematic representation of optical monitoring of the degradation process of the SF microsphere by an enzyme. (i) Plots of V/V0 of the SFmicrosphere versus the incubation time under H2O (black) and aqueous solutions of proteinase K (blue) and protease XIV (red). Reproduced from ref. 60(a–f) and 61 (g–i) with permission from the Royal Society of Chemistry, Copyright (2021) and Copyright (2023).Review Materials HorizonsOpen Access Article. Published on 24 June 2024. Downloaded on 7/16/2024 5:00:20 AM.  This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.View Article Onlinehttp://creativecommons.org/licenses/by/3.0/http://creativecommons.org/licenses/by/3.0/https://doi.org/10.1039/d4mh00218kThis journal is © The Royal Society of Chemistry 2024 Mater. Horiz., 2024, 11, 3203–3212 |  3209optical sensors, optical resonators and lasers, optical wave-guides, optical logic gates, and electronic transistors. By utiliz-ing the characteristics of natural biodegradable polymers, bio-and environmentally-friendly devices can be developed.4.1. Self-assembled silk fibroins for optical sensingSilk fibroin (SF) is a natural protein produced by the mulberrysilkworm (Bombyx mori). It is a historically important mer-chandise, especially in medieval times, when it was considereda luxurious fabric. Due to its high mechanical properties, ratherhigh refractive index (B1.54) and hygroscopic properties, aswell as high biocompatibility, SF is utilized for various applica-tions as biomedical material,50 such as for optics and sensing.For example, Malinowski et al. prepared SF films with hightransparency (493%) and high haze (465%), which enhancedthe silicon photodiode efficiency by 14.9%.51 Furthermore, Liet al. utilized SF thin film with sub-micron thick as humiditysensing, where the increase in the film thickness by moistureadsorption created a large redshift in the reflectance peak withoptical interference in the film.52Optical resonators are valuable for sensing applications withhigh sensitivity.53–56 Xu et al. fabricated a microtoroidal struc-ture from SF with a diameter of 80 mm.57 The toroidal diskacted as a whispering gallery mode (WGM) optical resonatorwith a high Q-factor in the order of 105. Utilizing the high Qresonator, the authors demonstrated thermal sensing with asensitivity of �0.72 nm K�1. When the disk was exposed toMeOH vapour and dried, the Silk I structure transformed to SilkII, thus leading to a much higher sensitivity of �1.17 nm K�1.This value is 8 times higher than previously reported values forsilica and polymer-based WGM thermal sensors.58,59Due to sharp PL peaks, WGM optical resonators are alsoutilized as highly sensitive humidity sensors (Fig. 8a).60 Usingthe water-in-oil mini-emulsion method with a natural surfac-tant, well-defined microspheres of SF are formed with anaverage diameter of 7.7 mm (Fig. 8b). The resultant SF micro-spheres, doped with a fluorescent dye, display clear WGMresonant peaks upon photoexcitation to a single microsphere(Fig. 8c). By increasing the relative humidity (RH) from 24 to95% at 25 1C, the diameter of the SF microspheres increaseswith moisture absorption, accompanying the redshift of reso-nant PL peaks (Fig. 8d). The peak shift shows an almost linearrelationship with the increase/decrease in the RH with asensitivity of 187 pm/% RH (Fig. 8e). The SF resonator main-tains its performance even at high humidity of 95% RH; goodrepeatability is seen upon switching the relative humiditybetween low (23% RH) and high RH (93%, Fig. 8f). Thehumidity sensing across a wide humidity range is suitable ina harsh environment.The peptide bonds in SF are selectively cleaved by an enzymecalled proteinase K. In general, the degradation process ismonitored by the weight loss of proteins in solution throughmixing with enzymes, centrifugation, extraction, drying, andweighing. However, it requires a gram-scale sample and takestime (several days to months). Additionally, it is difficult toinvestigate the beginning of the degradation process. Using theSF microsphere resonator, the degradation process of proteinscan be monitored precisely (Fig. 8g).61 When a buffer solutioncontaining proteinase K is added into a solvent containing theSF microspheres that are mounted on a quartz substrate(Fig. 8h), the peak shift of the WGM PL starts at 40 min afterthe addition of proteinase K (Fig. 8i). The peak shift is con-verted into the volume loss of the microsphere, indicating thecleavage of the SF protein by proteinase K.Apart from proteins, several optical microresonators fromnatural polymers have been reported. For example, Wei et al.reported WGM microlasers made of microspheres of potatostarch that had been doped with a fluorescent dye.62 The lasingpeaks shift upon dehydration, where the structural transforma-tion occurs from native B-type starch into A-type starch withdouble helix conformation. Recently, Suharman et al. reportedthermally tolerant microsphere resonators from quasi-naturalFig. 9 (a) Matrix of optical gate operations and outputs, schematicrepresentations, and corresponding optical and fluorescent microscopyimages of the combination of switching and NOT gates. The microspheresare arranged on two dragline fibers. Upon photoexcitation of the micro-sphere on the left, blue-color PL is generated, which passes through thedragline fiber and reaches the microsphere at the center. The centremicrosphere works as an optical gate, which controls any further trans-mission of light to output microspheres on the right. (b) Structure of OFETfabricated with albumen dielectrics with egg white; the schematic drawingof the denaturation of albumen protein and the crosslinking reaction underthermal treatments. Reproduced from ref. 65 (a) and 66 (b) with permissionfrom Wiley-VCH, Copyright (2023) and Copyright (2011).Materials Horizons ReviewOpen Access Article. Published on 24 June 2024. Downloaded on 7/16/2024 5:00:20 AM.  This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.View Article Onlinehttp://creativecommons.org/licenses/by/3.0/http://creativecommons.org/licenses/by/3.0/https://doi.org/10.1039/d4mh00218k3210 |  Mater. Horiz., 2024, 11, 3203–3212 This journal is © The Royal Society of Chemistry 2024poly(lactic acid).63 Upon mixing poly(L-lactic acid) and poly-(D-lactic acid), polymers form a stereocomplex, which enhancesthermal stability. As a result, optical resonator properties arepreserved even at 230 1C, which is 70 1C higher than the acceptabletemperature for homochiral microspheres of poly(L-lactic acid) orpoly(D-lactic acid).4.2. Optical and electronic gate operations of natural proteinsOptical fibres require high transparency, high refractive index,and high mechanical and thermal stability, along with goodprocessability. Polymer optical fibres have received increasingattention due to their high flexibility and processability. Syn-thetic polymer fibres are often utilized for transmitting opticalsignals,64 but natural fibres with high transparency are alsoutilizable. For example, Hendra et al. demonstrated the operationof an optical logic gate using fluorescent optical resonatorsthat were interconnected with dragline spider silk microfibres.65The optical loss coefficient of the natural dragline fibre was eva-luated to be 0.03 dB mm�1, which is superior to that of polystyrene(PS) microfibres made by hand spinning (0.13 dB mm�1).64By combining photoswitchable fluorescent microresonators, theswitching gate and a NOT gate, their combined operations aredemonstrated (Fig. 9a).For electronic gates, Chang et al. utilized chicken egg white,also called chicken albumen, as a dielectric layer of an organicfield-effect transistor (OFET) (Fig. 9b).66 Using pentacene andC60 as hole- and electron-transporting layers, FET operationswork with the hole and electron mobilities of 0.09 and0.13 cm2 V�1 s�1, respectively. The dielectric properties ofchicken albumen are more than double those of PS and poly-methylmethacrylate (PMMA). The FET operation is observedusing a flexible polyethylene naphthalene (PEN) substrate withhigh reproducibility after bending the substrate. Furthermore,complementary inverter operation was demonstrated. Wanget al. reported silk fibroin as a dielectric layer of flexible OFETwith pentacene as an active layer and polyethylene terephtha-late (PET) as the flexible substrate.67 The field-effect mobilitywas as high as 23.2 cm2 V�1 s�1 with a low operation voltageof �3 V.5. ConclusionsThis article comprehensively reviews recent progress in thedesign of peptide-based self-assembled materials. Given theability of the peptides to control 1D, 2D and 3D orientations offunctionalities attached, they are attractive scaffolds to designmaterials for various purposes, such as catalysts, sensingas well as biomedical treatments. Strategies, such as (1) sideresidue functionalization, (2) hybridization of the self-assembledform with other materials and (3) self-assembly into non-natural3D structures, as described in this review, allowed the develop-ment of non-intrinsic properties and functions of the peptides.Since the structures and properties of the peptides have beenimproved through repetitive biotic and prebiotic selection pro-cesses, the fabrication of peptide-based materials can be regardedas a long-term nature–human collaboration, which will keepproviding fruitful products as it has been already. State-of-the-art studies afford various applications of the peptides and theirassemblies, including cyclic peptides, mainly for their drug,pharmaceutical and biomedical applications.68–73 However, byfully utilizing the inherent properties, such as precise self-assembly and self-organization, self-assembled peptides can beutilized as materials for practical applications for optics andelectronics in biologically and environmentally friendly manners.The cost of materials, processing, durability, and useful propertiesare the next important issues for utilizing peptide assemblies asfuture materials and device applications.Conflicts of interestThere are no conflicts to declare.AcknowledgementsKT acknowledges the World Premier International ResearchCenter (WPI) Initiative on Materials Nanoarchitectonics fromMEXT, Japan and KAKENHI (JP23K04844) for funding. 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