Advertisement

2D bio-nanostructures fabricated by supramolecular self-assembly of protein, peptide, or peptoid

  • Weihong Zhang
  • Peng YangEmail author
Review
  • 192 Downloads

Abstract

Biomolecular self-assembly is a promising strategy for fabricating two-dimensional (2D) nanostructures such as sheets, films, lattices, or membranes. In this paper, we summarize the recent development of 2D bio-nanostructures that are formed by supramolecular self-assembly of protein, peptide, or peptoid, respectively. Specific focus is given on the formation mechanisms and the structures as well as functionality of the 2D bio-nanostructures. Besides, some typical applications of 2D bio-nanostructures have been listed. At last, the potential research direction of 2D bio-nanostructures is discussed.

Graphical abstract

Recent developments of 2D bio-nanostructures formed by supramolecular self-assembly of protein, peptide, or peptoid are reviewed.

Keywords

2D materials Bio-nanostructures Amyloid assembly Protein Peptide/peptoid 

1 Introduction

2D nanostructures are emerging as an important material class in recent years. They have broad application prospect in various fields of electronics, optics, sensing, actuating, catalysis, energy, etc. [1, 2, 3, 4, 5]. Compared to the low dimensional and three-dimensional nanostructures, 2D nanostructures possess higher superficial area to volume ratios resulting from their extreme aspect ratio. Thus, they present a variety of interesting properties and can provide a general platform on which to display an enormous diversity of functionalities [6, 7, 8].

In contrast to common inorganic or organic nanostructures formed by limited source, biomacromolecule-derived 2D bio-nanostructures, for instance, lattices, sheets, arrays, membranes, films, and ribbons by self-assembly of proteins, peptides, or peptoids, have attracted interests of many researchers [9, 10, 11].

Herein, we describe the recent development of proteins, peptide, or peptoid as building blocks to from 2D bio-nanostructures through supramolecular self-assembly and highlight the formation mechanisms and the structures as well as functionality of the 2D bio-nanostructures.

2 2D bio-nanostructures derived from self-assembly of proteins

Complex but highly ordered various architectures derived from protein self-assembly are the best form of supreme wisdom of nature. In the field of biological materials, well-defined 2D architectures derived from designed assembly of proteins can contribute to tailor materials with new physical and chemical properties.

Surface layer (S-layer) proteins are promising building blocks in nanotechnology for they not only create a cell-surface layer architecture in both archaea and bacteria but also can easily self-assemble into a single layer of crystalline nanostructure in vitro.

Moll et al. [12] fused streptavidin to a crystalline bacterial cell S-layer protein and exploited these S-layer-streptavidin fusion proteins as building blocks to fabricate 2D protein lattice or sheets. Furthermore, chimeric S-layer with the ability to bind with biotinylated ferritin was designed.

Similarly, Wang et al. [13] genetically fused the S-layer protein of Bacillus anthracis EA1 with methyl parathion hydrolase (MPH) and constructed a new EA1-based 2D nanostructure through self-assembly in vitro. When applied in detecting anthrax-specific antibodies in serum samples, the new nanostructure of S-layer–enzyme conjugation showed excellent performances in both detection sensitivity and enzymatic stability of MPH.

Based on the understanding that the nanostructures of self-assembling proteins were strongly influenced by the solution conditions, Rad and co-workers [14] established the diagrams coupled with modeling of the self-assembly process of SbpA, a S-layer protein from the insect pathogen Lysinibacillus sphaericus, in a large range of concentrations of SbpA and Ca2+. The diagrams mapped by high-throughput light scattering showed that both nanosheet yield and size varied as a function of time and Ca2+ concentration. Moreover, calcium ions were found to mediate specific as well as nonspecific interactions during the course of self-assembly.

Besides, the self-assembly behaviors of many other kind of proteins had been investigated in-depth. Some valuable research efforts are introduced as follows.

To eliminate clashes at the newly introduced interface and fabricate protein 2D lattices more easily, Matthaei et al. [15] designed a kind of hexamer referred to as TTM (Fig. 1) by combining fusion of two copies of point-symmetric building blocks and side-chain truncations. The experimental results demonstrated that the design predictions were realized completely, namely, TTM could self-assemble into flat 2D arrays with p3 symmetry upon addition of calcium ions. And the lattices were 5 nm high, 7.25 nm lattice constant, and the characteristic length of the arrays could exceed 100 μm. The authors expected that this TTM platform will surpass S-layers in practical application.
Fig. 1

a Schematic illustration of structure of a TTM hexamer. b Schematic of 2D lattices formation by TTM self-assembly. Reproduced with permission from Ref. [15]. Copyright 2015 American Chemical Society

Brodin et al. [16] developed a method by using directional metal coordination bonds to control protein self-assembly. As shown in Fig. 2, they demonstrated that a designed variant of the monomeric electron transfer protein cytochrome cb562, referred to as RIDC3, could self-assemble into 1D nanotubes or 2D and 3D arrays just through Zn2+ and pH coordination. Further study [17] by them showed that 2D Zn-directed RIDC3 assemblies could maintain their structural stability even in several polar organic solvents or at high temperature (~ 90 °C). It is well to be reminded that helical 1D RIDC3 nanotubes could convert into multilayered 2D arrays just through heating above 70 °C.
Fig. 2

Schematic view of Zn2+-mediated self-assembly of monomeric RIDC3 into 1D nanotubes and 2D and 3D arrays. Reprinted with permission from Ref. [16]. Copyright 2012 Macmillan Publishers Limited, part of Springer Nature

By taking advantage of both directional metal-protein coordination and nonspecific protein-protein interactions, Bai et al. [18] developed a solution to control the self-assembly behaviors of protein accurately. A series of highly ordered S-transferase (GST) nanorings with different diameters had been obtained through altering the Ni2+ strength of the solution in a certain range.

Amyloid fibrils generally possess very high mechanical strength and good adhesion capability to various substrates. By using simple assembly techniques, amyloid fibrils can create 2D amyloid nanostructures in diversity. For instance, the manipulation of the assembly of a classical globular protein, lysozyme, could serve as a kind of typical amyloid aggregation structure.

As shown in Fig. 3, Knowles et al. [19] fabricated free-standing amyloid protein films through a two-step self-assembly process using hen egg white lysozyme as raw material. The well-ordered films were so rigid that their Young’s modulus reached up to 5–7 GPa. Meanwhile, it can be functionalized with fluorophores just by simple mixing and stirring.
Fig. 3

a Schematic of the formation process of nanostructured protein film through two-step self-assembly. b AFM images of the lysozyme fibrils. c SEM images of the resulting free-standing protein film. Reprinted with permission from Ref. [19]. Copyright 2010 Macmillan Publishers Limited, part of Springer Nature

In recent years, much significant progress on the theory and applications of amyloid-like protein assembly has been made by Yang’s group [20, 21, 22, 23, 24, 25, 26]. With deeply understanding the mechanism of the novel phase transition process of lysozyme, they discovered that the amyloid-like assembly of typical globular proteins, e.g., lysozyme could be rapidly achieved after efficiently reducing their disulfide bonds by Tris (2-Carboxyethyl) phosphine (TCEP) under quasi-physiological condition. TCEP is known for its good reduction ability of disulfide bonds of biomolecules in various environments [20]. When mixing TECP with lysozyme in a neutral buffer, TCEP could effectively break down the disulfide bond of lysozyme chain; meanwhile, α-helix of native lysozyme was unfolded into β-sheet structure [21], resulting in the formation of insoluble amyloid nanospheres. Therefore, with stepwise nucleation and fusion, 2D assembled nanofilm of phase-transitioned lysozyme (PTL) will be formed gradually if the concentrations of lysozyme and TECP are enough.

As shown in Fig. 4, the PTL film could be coated or transferred on the surface of various materials [24]. What make their research different is that a macro-scale size free-floating film could be fabricated only by simple one-step aqueous assembly in minutes. In addition, the film can be readily transferred onto solid surface with stable adhesion strength just by mere solution-dipped method or a simple contact-printing strategy assisted by agarose hydrogel.
Fig. 4

a The strategies to form PTL film on the solid/liquid interface. b Schematic representation of PTL film formation at the vapor/liquid interface. c The schematic illustration of depositing the PTL film onto water-sensitive substrates by using contact-printing technique. Reprinted with permission from Ref. [24]. Copyright 2016 WILEYVCH Verlag GmbH & Co. KGaA, Weinheim

It is worth mentioning that the interfacial adhesion mechanism of such new kind of amyloid-like PTL nanofilm onto many model surfaces have been proposed by Yang’s group [25]. As shown in Fig. 5, between different polar or nonpolar abiotic surfaces and PTL film, there are different binding strengths, such as metal-sulfur coordination bonding, hydrogen bonding, electrostatic interaction/hydrogen bonding, and hydrophobic interaction. Besides the bondings or interactions mentioned above, the surface roughness can influence the adhesion capability of the PTL film. The numerical values of root mean square (RMS) measured by atomic force microscopy (AFM) has been used to express the surface roughness of the nanofilm [24]. And RMS of the film can be flexibly tuned by incubation time, the concentrations of TCEP and lysozyme, or pH of the solution. In general, the larger RMS leads to higher adhesion.
Fig. 5

Schematic representation of different kinds of main adhesive interactions between diverse material surfaces and PTL film. Reprinted with permission from Ref. [25]. Copyright 2018 Elsevier B.V

Very recently, Yang’s group reported their latest research on biomimic application of the PTL nanofilm [26]. As shown in Fig. 6, due to surface-anchored abundant functional groups, such as alkyl, carboxyl, amine, and hydroxyl, the PTL film was used as an effective template to bind with calcium ions through the chelation with the carboxyl as well as hydroxyl groups in the surface of the film. The further results obtained by X-ray photoelectron spectroscopy (XPS) found that the intensities of carboxyl and hydroxyl to bind with Ca2+ were 1.61 × 10−8 mol cm−2 and 3.5 × 10−9 mol cm−2, respectively. The nucleation as well as growth of hydroxyapatite (HAp) crystals was facilitated greatly by the presence of Ca2+ based on electrostatic interaction.
Fig. 6

Schematic illustration of fabricating course of HAp on the PTL nanofilm. Reproduced with permission from Ref. [26]. Copyright 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

As a result, HAp on the PTL coating acted as intermediate adhesion layer and presented excellent bonding stability to meet general load requirements when be applied on artificial bone and tooth. Cytotoxicity assays indicated that PTL nanofilm as well as HAp on the PTL nanofilm supports good biocompatibility and cytocompatibility toward rat bone marrow mesenchymal stem cells (rBMSCs). Subsequent animal tests on subcutaneous implantation in a rat model indicated that this biomaterial presented a favorable in vivo osteoconductivity.

Other proteins such as silk protein, β-lactoglobulin are also largely exploited for amyloid-inspired assembly and materials. In this context, taking advantage of polymorphic crystalline structure of silk protein, Kim and coworkers [27] prepared thin silk films with controlled thickness by spin coating aqueous silk solution on a substrate. And these silk films were further used as natural and biofunctional resist for electron-beam/photo-lithography. As shown in Fig. 7, β-lactoglobulin amyloid fibrils decorated by Au or Pd nanoparticles have been prepared by Bolisetty et al. [28]. And a hybrid amyloid membrane with the capability of continuous flow catalysis was fabricated by vacuum filtering these composite fibrils on top of nitrocellulose membranes. The results also showed that the amyloid fibril templates could effectively enhance the catalytic activity of the metal nanoparticles. The hybrid membranes were found to perform remarkably well in wet catalysis, e.g., 4-nitrophenol could be catalyzed and transformed completely into 4-aminophenol only need to flow through the membrane.
Fig. 7

a Schematic representation of β-lactoglobulin amyloid fibrils. b The preparation of Au or Pd nanoparticles decorated amyloid fibrils by using redox reaction. c The hybrid filter membrane reactor. Reprinted with permission from Ref. [28]. Copyright 2015 American Chemical Society

3 2D bio-nanostructures derived from self-assembly of peptides

Just like proteins, a peptide is another major molecular scaffold material in fabricating 2D bio-nanostructures by self-assembly. Moreover, benefit from shorter chains and smaller molecular weights, peptides are more likely to spontaneously self-assemble into nanoarchitectures than proteins. Importantly, peptides can be synthesized on a large scale by conventional chemical techniques.

As early in 1993, Zhang et al. [29] found that a 16-residue peptide [(Ala-Glu-Ala-Glu-Ala-Lys-Ala-Lys)2] could spontaneously assemble to form a macroscopic membrane in aqueous solution upon the addition of salts. And the stability of the membrane was so high that it did not dissolve in hot, acidic, or alkaline solutions as well as some frequently-used solvents, nor did it dissolve upon addition of enzymes.

Similarly, Hamley and coworkers [30] reported on the formation of free-floating nanosheets with 3 nm thick by an amphiphilic peptide (Ala)6(Arg) in aqueous solution. They discovered that the concentration of peptide was the decisive factor in the course of self-assembly, that is, ultrathin sheets without β-sheet would form at low concentration (below 2 wt%), whereas helically wrapped ribbons coexisting with nanotubes would appear at 15 wt% and above accompanying with β-sheet formation. Whereafter, the self-assembly behavior of surfactant-like peptide (Ala)6-(Asp) (A6D) in aqueous solution especially when hexamethylene diamine was added into the system at different molar ratio was investigated by Hamley’s research group [31]. They found that acid-coated multiple ordered nanostructures, such as nanosheet and bicontinuous network structures, could be obtained by adding appropriate amount of diamine. However, the self-assembled structure would be lost completely at 2:1 M ratio of diamine to A6D. So, addition of a diamine is an effective means to modulate the self-assembly behavior of A6D.

Taking the peptide KLVFFAE (named Aβ16–22) as research object, Pan et al. [32] systematically studied the effect of hydrated electrons on peptide self-assembly. They discovered that uniform and ultrathin films with well-defined orientation could be fabricated through self-assembly of Aβ16–22 after treating by plasma for a few minutes and incubation in an incubator at 37 °C for a certain time. Based on a series of instrument characterization and discussions, a formation mechanism for the peptide films through three possible patterns of organizing the fibrils has been proposed (Fig. 8). That is, for three different patterns, the fibrils primarily organized through C-C and N-(hydrated electron)-N interactions, C-N interactions, and C-C and N-N interactions, respectively.
Fig. 8

Formation mechanism for the films through three possible patterns of organizing the fibrils. Reprinted with permission from Ref. [32]. Copyright 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Dai and co-workers [33] found that Italian familial Aβ16–22 (KLVFFAK), a key amyloid-forming heptapeptide, could self-assemble into a 2D nanosheet in aqueous solution. Based on the experimental and computational results, a starting model for molecular dynamics simulation and a structural model of the KLVFFAK nanosheet were proposed (Fig. 9); the model indicated that the KLVFFAK nanosheet expanded in two dimensions, one was the fibril axis (axis a′) and the other was zippering axis (axis b′). Furthermore, the interactions between molecules were demonstrated clearly, that is, the peptides were stacked via hydrogen bonds along axis a′, on the other hand, the β-sheets stacked in face to back pattern via the side-chain steric hydrophobic interactions along axis b′.
Fig. 9

Structural model of the KLVFFAK nanosheet. Reproduced with permission from Ref. [33]. Copyright 2015 National Academy of Sciences

Besides, they further designed experiments to confirm that KLVFFAK nanosheet can effectively enhance retroviral gene transduction. As shown in Fig. 10, viral particles attachment on the surface of KLVFFAK nanosheet can be observed clearly by electron microscope.
Fig. 10

a Sketch of virus particles attaching on nanosheets. b TEM images of virus particles attaching on KLVFFAK and KLVFFAR nanosheets. Reproduced with permission from Ref. [33]. Copyright 2015 National Academy of Sciences

Considering limited source of native peptide, active design of peptide sequences seems to be a good choice to obtain desired assembly effect or more promising functionality. Jang and co-workers [34] prepared many sequence-specific peptides by systematically introducing repeating tyrosine units into peptides with various lengths. Some peptides designed by them, such as YYACAYY (H-Tyr-Tyr-Ala-Cys-Ala-Tyr-Tyr-OH), YYCYY, and YYCYYY, could self-assemble into a 2D film and facet successively on the top of a water droplet. Facet-forming mechanism was shown in Fig. 11. YYACAYY peptides floated on air/water interface, hydrophobic tyrosine regions of them would prefer to move into the air, and the peptides film and facet were formed gradually by multiple self-assembly and migration by peptides and peptide rafts at the air/water interface. Furthermore, the experimental result confirmed that this kind of tyrosine-containing peptide film could trigger or enhance chemical/electrochemical reactions for redox activity of tyrosine.
Fig. 11

a Molecular structure of YYACAYY. b Microphotographs of a water droplet at different incubation times. c Schematics of the facet-forming mechanism with the YYACAYY solution. Reproduced with permission from Ref. [34]. Copyright 2014 Macmillan Publishers Limited

Two years later, the design and self-assembly performance of another peptide sequence YFCFY, where Y represents tyrosine, F represents phenylalanine, and C refers to cysteine, was reported by the same research group [35]. Different from YYACAYY could self-assemble only in the buffering conditions; YFCFY can assemble even in pure water. Moreover, the final assembly form of YFCFY at air/water interface is always flat sheet regardless of the initial status if it is a fibril-aggregated, rough film or uniformly packed.

Jiang et al. [36] reported that two molecularly programmed collagen-mimetic peptide sequences, named NSI and NSII, self-assembled into 2D nanosheets with an ordered internal structure. And that the thickness of nanosheets could be controlled through the peptide length and terminal functionality. However, the resultant nanosheets were heterogeneous in both sheet-growth dimension and sheet stacking dimension. In order to solve this problem, a new collagen-mimetic peptide, NSIII, was designed by the same research team and a highly homogeneous population of nanosheets was obtained [37]. As shown in Fig. 12, there are distinct differences in amino acid sequences between NSI and NSIII.
Fig. 12

a Amino acid sequences of peptides NSI and NSIII. b Structures of imino acid derivatives. Reproduced with permission from Ref. [37]. Copyright 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Soon afterwards, in order to promote the formation of multilayer structures, Jiang et al [38] designed two collagen-mimetic peptides, CP+ and CP (Fig. 13). Because the self-assembly speed of CP+ nanosheets was more faster than that of CP nanosheets, in practice, CP+ peptides always assembled without template and CP peptides self-assembled with CP+ monolayers as templates, which led to the formation of CP-/CP+/CP multilayer structures.
Fig. 13

Amino acid sequences and nanosheets assemblies from CP+ and CP peptides. Reproduced with permission from Ref. [38]. Copyright 2015 American Chemical Society

Except for the intensive study on the formation mechanisms and basic application of self-assembling 2D peptide nanostructure, some researchers used the unique 2D nanostructure to solve the problems which existed in other areas. Some examples are listed below.

To enhance the capacity to resist the nonspecific protein adsorption on the surfaces of poly (dimethylsiloxane) (PDMS), Yu et al. [39] developed a modification method based on self-assembling of an ionic complementary peptide EAR16-II. Upon low concentrations of carbohydrates, this peptide was apt to self-assemble into an amphipathic film on PDMS surfaces regardless if the exact wettability of PDMS is native hydrophobic or plasma-oxidized hydrophilic. The schematic of the structure of amphipathic film fabricated by EAR16-II was shown in Fig. 14. Moreover, the interactions of EAR16-II with the PDMS surface as well as the antifouling capability of the peptide coatings at a molecular level had been explained by the schematic model. According to the results presented by the authors, the self-assembled EAR16-II coatings can greatly improve the capacities of protein-repelling and blood compatibility of PDMS.
Fig. 14

Amphipathic structure of EAR16-II molecular and schematic model of explaining the antifouling mechanism of EAR16-II coatings. Reprinted with permission from Ref. [39]. Copyright 2015 American Chemical Society

Pan et al. [40] fabricated a hybrid EY/Pt/Film assisted by plasma to induce peptide self-assembly. Just irradiated by visible light, the EY/Pt/Film showed outstanding catalytic activity for photocatalytic water splitting and CO2 reduction (Fig. 15). In this catalytic system, flexible self-assembled biofilm acted as an efficient transfer of the photoinduced electrons.
Fig. 15

Schematic illustration of photocatalytic course based on the hybrid film. Reprinted with permission from Ref. [40]. Copyright 2015 American Chemical Society

4 2D bio-nanostructures derived from self-assembly of peptoids

Peptoid is a novel class of highly designable and biomimetic heteropolymers [41]. Different from the structure of peptides, peptoids are poly(N-substituted glycines) in which the side chains are attached to the nitrogen rather than the α-carbon [42]. They can fold into higher order–specific protein-like structures but with the ability of resisting to proteolysis [43]. Peptoids are designed to act as typical representative of versatile biomimetic materials in the field of nanobioscience due to the synthetic flexibility, robustness, and ordering at the atomic level [44]. So, peptoid is one of the ideal candidates to create 2D bio-nanostructures.

A number of processes for different peptoid synthesis and self-assembly into 2D nanosheets have been investigated [44, 45, 46, 47, 48, 49, 50, 51, 52]. Tran et al. [44] described the overall synthesis process of sequence-specific peptoid polymers by solid-phase sub-monomer synthesis method in detail. And the protocol to form highly ordered nanosheets from an amphiphilic 36-mer peptoid was presented as well.

As shown in Fig. 16, Nam and coworkers [45] prepared a kind of free-floating ultrathin nanosheets through mixing two kinds of oppositely charged and sequence-specific peptoids with 1:1 ratio in aqueous solution.
Fig. 16

Schematic illustration of 2D nanosheets formed from two oppositely charged peptoid polymers. Reprinted with permission from Ref. [45]. Copyright 2010 Macmillan Publishers Limited

Based on designing five kinds of lipid-like peptoids, named Pep1-Pep5, stable membrane-mimetic 2D nanomaterials were achieved through self-assembly of the peptoids by Jin [46] and Jiao et al. [47] Just like real bilayer cell membranes, the peptoid membranes could respond to external stimuli, coat surfaces in single layers as well. More excitingly, the heavily scratched 2D peptoid membranes could self-repair when they were in certain conditions, such as introduction peptoid-containing solution and suitable pH. A number of factors which concern the rate of repair, such as charge state and wettability of the surface, peptoid headgroups, the concentration of the solution used for repair, were studied systematically by the authors.

Shi et al. [48] fabricated a free-standing, ultrathin crystalline nanosheet from self-assembly of poly-(ethylene glycol)-block-poly(N-octylglycine) (PEG-b-PNOG). As demonstrated in Fig. 17, the authors found that PEG-b-PNOG can assemble into a series of hierarchical nanostructures in the sequence of sphere, cylinder, and nanosheet driven by the crystallization of PNOG domains when they are in ethanol at a certain concentration. The contribution of this work is that the researchers discovered the synthetic polypeptoid-based diblock copolymers in selective solvents can mimic the pathways of protein crystallization to form the hierarchical nanostructure through a multiple-step strategy.
Fig. 17

Structural formula and ordinal supermolecule assembling bodies of PEG-b-PNOG. Reprinted with permission from Ref. [48]. Copyright 2018 American Chemical Society

Sanii et al. [49] proposed a potentially general mechanism for the 2D nanomaterial synthesis of peptoids (Fig. 18c). They found that the area of air-water interface would change greatly when a sealed glass vial partially filled with peptoid solution, slowly rotated from nearly horizontal to an upright position (Fig. 18a), and the high compression ratio during the rotation would make peptoid monolayer collapse into stable 2D nanosheets with high yielding and cyclical deformation. They considered that the compression of air-water interface during cyclical rotation supplied the continuous energy into the system, which was then adopted by peptoid monolayers to collapse them into more stable, free-floating nanosheets.
Fig. 18

a Area changes of air-water interface while a half-full vial is rotated from horizontal to vertical. b End-on view of the vial-rocking device during a rotation. c Schematic illustration of peptoid nanosheet formation through surface compressions. d Fluorescence microscope image of nanosheets. Reprinted with permission from Ref. [42]. Copyright 2011 American Chemical Society

Kudirka et al. [50] designed two kinds of single-chain peptoid with different sequences; the charged residues of them were configurated according to alternating patterning and block patterning, respectively. Then, nanosheets with higher order structures have been obtained by using the same vial-rocking device to Sanii et al.’s work [49]. The two nanosheets were confirmed to display different sensitivities to pH and chemical denaturants due to their different block charge design.

Differing from general knowledge that nanosheets prefer to form at the air-water interface, Robertson et al. [51] confirmed that peptoid nanosheets could be formed at oil-water interface. And the detection results of vibrational sum frequency spectroscopy demonstrated that an ordered peptoid monolayer formed at oil-water interface mainly by means of electrostatic interactions.

Based on the above systematic study, Sanii et al. [52] proposed a detailed mechanism model that peptoid polymers self-assembled into nanosheets at an air-water or oil-water interface. Moreover, the sequential order of several of structure-determining steps was pointed out one by one. Their results contributed to the insight into the general strategy of accelerating the assembly of 2D nanomaterials by using planar fluid interfaces.

Aside from the synthetic methods and assembly mechanisms of peptoids, the functionalizations and practical applications of peptoid nanosheets have been put into effect by many researchers [53, 54, 55]. In order to make peptoid nanosheets possessing the ability of protein recognition like cellular membrane, Battigelli et al. [53] functionalized the surface of peptoid nanosheets with different saccharide groups in a multivalent disposition at a controlled density (Fig. 19). The test results confirmed that the engineered nanosheets can selectively bind multivalent lectins, concanavalin A and wheat germ agglutinin. In addition, the system could be acted as sensor for detecting threat agents (such as toxin) if the peptoid nanosheets were bonded with appropriate ligands.
Fig. 19

Schematic diagram of peptoid nanosheet with the ability of protein recognition. Reprinted with permission from Ref. [53]. Copyright 2018 American Chemical Society

In view of abundant carboxylic acid groups in their surfaces and easy synthesis in high yield, Jun et al. [54] took free-floating zwitterionic peptoid nanosheets as a 2D platform to prepare amorphous calcium carbonate (ACC) films. As shown in Fig. 20, the whole courses of nacre mimetic mineralization were concise and effective; thus, peptoid nacre synthons with about 10 nm layers of ACC on each face were obtained.
Fig. 20

Schematic illustration of fabricating peptoid-based ACC. a Molecular structure of the peptoid. b Nanosheet with rich carboxyls assembled by the peptoid. c Free-floating mineralized nanosheet. d Organic/inorganic composite material generated by stacking and crystallizing of mineralized nanosheets. Reprinted with permission from Ref. [54]. Copyright 2015 Royal Society of Chemistry

Another typical practical application of peptoid nanosheets has been attempted by Olivier and coworkers [55]. They designed and synthesized a kind of antibody-mimetic materials based on functionalized nanosheets that were fabricated by self-assembling aggregates of peptoid polymers with specific sequences. Compared with native antibody, peptoid nanosheets possessed the advantages of higher stability, cheap raw material sources, additional functionalities, and so on.

Until now, peptoids belong to a side-chain-dominated system, and thus lack both chirality and the hydrogen bond donor in their backbone as well. So, more opportunities and possibilities can be offered to design new molecular structures and diverse properties. Compared with natural proteins and peptides, the feature of designable ability at molecular level makes peptoids seem to be suitable for fabricating highly tunable 2D nanostructures by self-assembly.

5 Summary and outlook

In this review, the recent progress in strategies for fabricating 2D bio-nanostructures through self-assembly of proteins, peptides, or peptoids have been summarized. We focused on the elucidation of the self-assembly mechanisms, hierarchical structure, and practical or potential applications of a series of 2D bio-nanostructures.

In our opinion, there are some areas that should be further investigated. One is fundamental knowledge of molecular dynamics or self-assembly kinetics of building blocks by using computer simulation techniques or other advanced instrument and equipment. The development in fundamental research will supply continuing inspiration and guidance for controllable growth and formation of 2D or 3D bio-nanostructures. Second, more efforts should be made on the discovery, selection, and development of proteins, peptides, or peptoids with specific sequence that are more suitable for nanofabrication. Last but not least, the new and valuable application of 2D bio-nanostructures should be exploited. The use of phase-transitioned lysozyme (PTL) nanofilm as an effective template to prepare artificial bone and tooth is an excellent example. As research continues, it is to be hoped that such extraordinary work in the field of biotechnologies and biomaterials will increase gradually.

Notes

Funding information

P.Y. thanks the funding from the National Natural Science Foundation of China (Grant Nos. 51673112 and 21374057), the 111 Project (Grant No. B14041), and Program for Changjiang Scholars and Innovative Research Team in University (Grant No. IRT_14R33) as well as Open Project of State Key Laboratory of Supramolecular Structure and Materials (Grant No. sklssm201727). W. Z. thanks the support of Natural Science Basic Research Plan in Shaanxi Province (No. 2016JM5024), China Postdoctoral Science Foundation (No. 2014M560747), and Scientific Research Project of Xianyang Normal University (No. 13XSYK017).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    You J, Li MJ, Ding BB, Wu XC, Li CX (2017) Crab chitin-based 2d soft nanomaterials for fully biobased electric devices. Adv Mater 29:1606895CrossRefGoogle Scholar
  2. 2.
    Liu W-D, Yang B (2017) Patterned surfaces for biological applications: a new platform using two dimensional structures as biomaterials. Chin Chem Lett 28:675–690CrossRefGoogle Scholar
  3. 3.
    Choi IY, Lee J, Ahn H, Lee J, Choi HC, Park MJ (2015) High-conductivity two-dimensional polyaniline nanosheets developed on ice surfaces. Angew Chem Int Ed 54:1–6CrossRefGoogle Scholar
  4. 4.
    Butler SZ, Hollen SM, Cao L, Cui Y, Gupta JA, Gutiérrez HR, Heinz TF, Hong SS, Huang J, Ismach AF, Johnston-Halperin E, Kuno M, Plashnitsa VV, Robinson RD, Ruoff RS, Salahuddin S, Shan J, Shi L, Spencer OMG, Terrones M, Wind W, Goldberger JE (2013) Progress, challenges, and opportunities in two-dimensional materials beyond graphene. ACS Nano 7:2898–2926CrossRefGoogle Scholar
  5. 5.
    Fang Y, Lv Y, Tang J, Wu H, Jia D, Feng D, Kong B, Wang Y, Elzatahry AA, Al-Dahyan D, Zhang Q, Zheng G, Zhao D (2015) Growth of single-layered two-dimensional mesoporous polymer/ carbon films by self-assembly of monomicelles at the interfaces of various substrates. Angew Chem Int Ed 127:8545–8549CrossRefGoogle Scholar
  6. 6.
    Zhang WH, Jiang BJ, Yang P (2016) Proteins as functional interlayer in organic field-effect transistor. Chin Chem Lett 27:1339–1344CrossRefGoogle Scholar
  7. 7.
    Wei T, Zhan WJ, Cao LM, Hu CM, Qu YC, Yu Q, Chen H (2016) Multifunctional and regenerable antibacterial surfaces fabricated by a universal strategy. ACS Appl Mater Interfaces 8:30048–30057CrossRefGoogle Scholar
  8. 8.
    Cao LM, Qu YC, Hu CM, Wei T, Zhan WJ, Y Q CH (2016) A universal and versatile approach for surface biofunctionalization: layer-by-layer assembly meets host–guest chemistry. Adv Mater Interfaces 3:1600600CrossRefGoogle Scholar
  9. 9.
    Wei G, Su Z, Reynolds NP, Arosio P, Hamley IW, Gazit E, Mezzenga R (2017) Self-assembling peptide and protein amyloids: from structure to tailored function in nanotechnology. Chem Soc Rev 46:4661–4708CrossRefGoogle Scholar
  10. 10.
    Dohno C, Makishi S, Nakatani K, Contera S (2017) Amphiphilic DNA tiles for controlled insertion and 2D assembly on fluid lipid membranes: effect on mechanical properties. Nanoscale 9:3051–3058CrossRefGoogle Scholar
  11. 11.
    Yan X, Zhu P, Li J (2010) Self-assembly and application of diphenylalanine-based nanostructures. Chem Soc Rev 39:1877–1890CrossRefGoogle Scholar
  12. 12.
    Moll D, Huber C, Schlegel B, Pum D, Sleytr UB, Sára M (2002) S-layer-streptavidin fusion proteins as template for nanopatterned molecular arrays. Proc Natl Acad Sci 99:14646–14651CrossRefGoogle Scholar
  13. 13.
    Wang XY, Wang DB, Zhang ZP, Bi LJ, Zhang JB, Ding W, Zhang XE (2015) A S-layer protein of bacillus anthracis as a building block for functional protein arrays by in vitro self-assembly. Small 11:5826–5832CrossRefGoogle Scholar
  14. 14.
    Rad B, Haxton TK, Shon A, Shin S-H, Whitelam S, Ajo-Franklin CM (2015) Ion-specific control of the self-assembly dynamics of a nanostructured protein lattice. ACS Nano 9:180–190CrossRefGoogle Scholar
  15. 15.
    Matthaei JF, DiMaio F, Richards JJ, Pozzo LD, Baker D, Baneyx F (2015) Designing two-dimensional protein arrays through fusion of multimers and interface mutations. Nano Lett 15:5235–5239CrossRefGoogle Scholar
  16. 16.
    Brodin JD, Ambroggio XI, Tang C, Parent KN, Baker TS, Tezcan FA (2012) Metal-directed, chemically tunable assembly of one-, two- and three-dimensional crystalline protein arrays. Nat Chem 4:375–382CrossRefGoogle Scholar
  17. 17.
    Brodin JD, Carr JR, Sontz PA, Tezcan FA (2014) Exceptionally stable, redox-active supramolecular protein assemblies with emergent properties. Proc Natl Acad Sci 111:2897–2902CrossRefGoogle Scholar
  18. 18.
    Bai YS, Luo Q, Zhang W, Miao L, Xu JY, Li HB, Liu JQ (2013) Highly ordered protein nanorings designed by accurate control of glutathione S-transferase self-assembly. J Am Chem Soc 135:10966–10969CrossRefGoogle Scholar
  19. 19.
    Knowles TPJ, Oppenheim TW, Buell AK, Chirgadze DY, Welland ME (2010) Nanostructured films from hierarchical self-assembly of amyloidogenic proteins. Nat Nanotechnol 5:204–207CrossRefGoogle Scholar
  20. 20.
    Yang P (2012) Direct biomolecule binding on nonfouling surfaces via newly discovered supramolecular self-assembly of lysozyme under physiological conditions. Macromol Biosci 12:1053–1059CrossRefGoogle Scholar
  21. 21.
    Wu ZF, Yang P (2014) Simple multipurpose surface functionalization by phase transited protein adhesion. Adv Mater Interfaces 2:1400401CrossRefGoogle Scholar
  22. 22.
    Wu Q, Gao AT, Tao F, Yang P (2018) Understanding biomolecular crystallization on amyloid like superhydrophobic biointerface. Adv Mater Interfaces 5:1701065CrossRefGoogle Scholar
  23. 23.
    Gao AT, Wu Q, Wang DH, Ha Y, Chen ZJ, Yang P (2016) A superhydrophobic surface templated by protein self-assembly and emerging application toward protein crystallization. Adv Mater 28:579–587CrossRefGoogle Scholar
  24. 24.
    Wang DH, Ha Y, Gu J, Li Q, Zhang LL, Yang P (2016) 2D protein supramolecular nanofilm with exceptionally large area and emergent functions. Adv Mater 28:7414–7423CrossRefGoogle Scholar
  25. 25.
    Gu J, Miao ST, Yan ZG, Yang P (2018) Multiplex binding of amyloid-like protein nanofilm to different material surfaces. Colloid Interface Sci Commun 22:42–48CrossRefGoogle Scholar
  26. 26.
    Ha Y, Yang J, Tao F, Wu Q, Song YJ, Wang HR, Zhang X, Yang P (2018) Phase-transited lysozyme as a universal route to bioactive hydroxyapatite crystalline film. Adv Funct Mater 28:1704476CrossRefGoogle Scholar
  27. 27.
    Kim S, Marelli B, Brenckle MA, Mitropoulos AN, Gil E-S, Tsioris K, Tao H, Kaplan DL, Omenetto FG (2014) All-water-based electron-beam lithography using silk as a resist. Nat Nanotech 9:306–310CrossRefGoogle Scholar
  28. 28.
    Bolisetty S, Arcari M, Adamcik J, Mezzenga R (2015) Hybrid amyloid membranes for continuous flow catalysis. Langmuir 31:13867–13873CrossRefGoogle Scholar
  29. 29.
    Zhang SG, Holmes T, Lockshin C, Rich A (1993) Spontaneous assembly of a self-complementary oligopeptide to form a stable macroscopic membrane. Proc Natl Acad Sci 90:3334–3338CrossRefGoogle Scholar
  30. 30.
    Hamley IW, Dehsorkhi A, Castelletto V (2013) Self-assembled arginine-coated peptide nanosheets in water. Chem Commun 49:1850–1852CrossRefGoogle Scholar
  31. 31.
    Hamley IW, Hutchinson J, Kirkham S, Castelletto V, Kaur A, Reza M, Ruokolainen J (2016) Nanosheet formation by an anionic surfactant-like peptide, and modulation of self-assembly through ionic complexation. Langmuir 32(40):10387–10393CrossRefGoogle Scholar
  32. 32.
    Pan Y-X, Liu C-J, Zhang S, Yu Y, Dong MD (2012) 2D-oriented self-assembly of peptide induced by hydrated electrons. Chem Eur J 18:14614–14617CrossRefGoogle Scholar
  33. 33.
    Dai B, Li D, Xi WH, Luo F, Zhang X, Zou M, Cao M, Hu J, Wang WY, Wei GH, Zhang Y, Liu C (2015) Tunable assembly of amyloid-forming peptides into nanosheets as a retrovirus carrier. Proc Natl Acad Sci 112:2996–3001CrossRefGoogle Scholar
  34. 34.
    Jang H-S, Lee J-H, Park Y-S, Kim Y-O, Park J, Yang T-Y, Jin K, Lee J, Park S, You JM, Jeong K-W, Shin A, Oh I-S, Kwon M-K, Kim Y-I, Cho H-H, Han HN, Kim Y, Chang YH, Paik SR, Nam KT, Lee Y-S (2014) Tyrosine-mediated two-dimensional peptide assembly and its role as a bio-inspired catalytic scaffold. Nat Commun 5:3665CrossRefGoogle Scholar
  35. 35.
    Lee J, Choe IR, Kim N-K, Kim W-J, Jang H-S, Lee Y-S, Nam KT (2016) Water-floating giant nanosheets from helical peptide pentamers. ACS Nano 10:8263–8270CrossRefGoogle Scholar
  36. 36.
    Jiang T, Xu C, Liu Y, Liu Z, Wall JS, Zuo X, Lian T, Salaita K, Ni C, Pochan D, Conticello VP (2014) Structurally defined nanoscale sheets from self-assembly of collagen-mimetic peptides. J Am Chem Soc 136:4300–4308CrossRefGoogle Scholar
  37. 37.
    Jiang T, Xu C, Zuo X, Conticello VP (2014) Structurally homogeneous nanosheets from self-assembly of a collagen-mimetic peptide. Angew Chem Int Ed 53:8367–8371CrossRefGoogle Scholar
  38. 38.
    Jiang T, Vail OA, Jiang ZG, Zuo XB, Conticello VP (2015) Rational design of multilayer collagen nanosheets with compositional and structural control. J Am Chem Soc 137:7793–7802CrossRefGoogle Scholar
  39. 39.
    Yu XL, Xiao JZ, Dang FQ (2015) Surface modification of poly (dimethylsiloxane) using ionic complementary peptides to minimize nonspecific protein adsorption. Langmuir 31:5891–5898CrossRefGoogle Scholar
  40. 40.
    Pan Y-X, Cong H-P, Men Y-L, Xin S, Sun Z-Q, Liu C-J, Yu S-H (2015) Peptide self-assembled biofilm with unique electron transfer flexibility for highly efficient visible-light-driven photocatalysis. ACS Nano 9:11258–11265CrossRefGoogle Scholar
  41. 41.
    Sun J, Zuckermann RN (2013) Peptoid polymers: a highly designable bioinspired material. ACS Nano 7:4715–4732CrossRefGoogle Scholar
  42. 42.
    Lau KHA (2014) Peptoids for biomaterials science. Biomater Sci 2:627–633CrossRefGoogle Scholar
  43. 43.
    Kirshenbaum K, Barron AE, Goldsmith RA, Armand P, Bradley EK, Truong KTV, Dill KA, Cohen FE, Zuckermann RN (1998) Sequence-specific polypeptoids: a diverse family of heteropolymers with stable secondary structure. Proc Natl Acad Sci 95:4303–4308CrossRefGoogle Scholar
  44. 44.
    Tran H, Gael SL, Connolly MD, Zuckermann RN (2011) Solid-phase submonomer synthesis of peptoid polymers and their self-assembly into highly-ordered nanosheets. J Vis Exp 57:1–7Google Scholar
  45. 45.
    Nam KT, Shelby SA, Choi PH, Marciel AB, Chen R, Tan L, Chu TK, Mesch RA, Lee B-C, Connolly MD, Kisielowski C, Zuckermann RN (2010) Free-floating ultrathin two-dimensional crystals from sequence-specific peptoid polymers. Nat Mater 9:454–460CrossRefGoogle Scholar
  46. 46.
    Jin H, Jiao F, Daily MD, Chen Y, Yan F, Ding Y, Zhang X, Robertson EJ, Baer MD, Chen C (2016) Highly stable and self-repairing membrane-mimetic 2D nanomaterials assembled from lipid-like peptoids. Nat Commun 7:12252CrossRefGoogle Scholar
  47. 47.
    Jiao F, Chen Y, Jin H, He P, Chen C-L, Yoreo JJD (2016) Self-repair and patterning of 2D membrane-like peptoid materials. Adv Funct Mater 26:8960–8967CrossRefGoogle Scholar
  48. 48.
    Shi ZK, Wei YH, Zhu CH, Sun J, Li ZB (2018) Crystallization-driven two-dimensional nanosheet from hierarchical self-assembly of polypeptoid-based diblock copolymers. Macromolecules 51(16):6344–6351CrossRefGoogle Scholar
  49. 49.
    Sanii B, Kudirka R, Cho A, Venkateswaran N, Olivier GK, Olson AM, Tran H, Harada RM, Tan L, Zuckermann RN (2011) Shaken, not stirred: collapsing a peptoid monolayer to produce free-floating, stable nanosheets. J Am Chem Soc 133:20808–20815CrossRefGoogle Scholar
  50. 50.
    Kudirka R, Tran H, Sanii B, Nam KT, Choi PH, Venkateswaran N, Chen R, Whitelam S, Zuckermann RN (2011) Folding of a single-chain, information-rich polypeptoid sequence into a highly ordered nanosheet. Pept Sci 96:586–595CrossRefGoogle Scholar
  51. 51.
    Robertson EJ, Olivier GK, Qian M, Proulx C, Zuckermann RN, Richmond GL (2014) Assembly and molecular order of two-dimensional peptoid nanosheets through the oil–water interface. Proc Natl Acad Sci 111:13284–13289CrossRefGoogle Scholar
  52. 52.
    Sanii B, Haxton TK, Olivier GK, Cho A, Barton B, Proulx C, Whitelam S, Zuckermann RN (2014) Structure-determining step in the hierarchical assembly of peptoid nanosheets. ACS Nano 8:11674–11684CrossRefGoogle Scholar
  53. 53.
    Battigelli A, Kim JH, Dehigaspitiya DC, Proulx C, Robertson EJ, Murray DJ, Rad B, Kirshenbaum K, Zuckermann RN (2018) Glycosylated peptoid nanosheets as a multivalent scaffold for protein recognition. ACS Nano 12(3):2455–2465CrossRefGoogle Scholar
  54. 54.
    Jun JMV, Altoe M, V P, Aloni S, Zuckermann RN (2015) Peptoid nanosheets as soluble, two-dimensional templates for calcium carbonate mineralization. Chem Commun 51:10218–10221CrossRefGoogle Scholar
  55. 55.
    Olivier GK, Cho A, Sanii B, Connolly MD, Tran H, Zuckermann RN (2013) Antibody-mimetic peptoid nanosheets for molecular recognition. ACS Nano 7:9276–9286CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Key Laboratory of Applied Surface and Colloids Chemistry, Ministry of Education, School of Chemistry and Chemical EngineeringShaanxi Normal UniversityXi’anChina
  2. 2.College of Chemistry and Chemical EngineeringXianyang Normal UniversityXianyangChina

Personalised recommendations