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.
The reversible in situ formation of a self‐assembly building block (naphthalenediimide (NDI)–dipeptide conjugate) by enzymatic condensation of NDI‐functionalized tyrosine (NDI‐Y) and ...phenylalanine‐amide (F‐NH2) to form NDI‐YF‐NH2 is described. This coupled biocatalytic condensation/assembly approach is thermodynamically driven and gives rise to nanostructures with optimized supramolecular interactions as evidenced by substantial aggregation induced emission upon assembly. Furthermore, in the presence of di‐hydroxy/alkoxy naphthalene donors, efficient charge‐transfer complexes are produced. The dynamic formation of NDI‐YF‐NH2 and electronic and H‐bonding interactions are analyzed and characterized by different methods. Microscopy (TEM and AFM) and rheology are used to characterize the formed nanostructures. Dynamic nanostructures, whose formation and function are driven by free‐energy minimization, are inherently self‐healing and provide opportunities for the development of aqueous adaptive nanotechnology.
Built through biocatalysis: 1D chiral charge‐transfer nanofibers were fabricated through the biocatalytic self‐assembly of naphthalenediimide amino acid/dipeptide conjugate acceptors and dialkoxy/hydroxy naphthalene donors. In the obtained aqueous hydrogels, the charge‐transfer‐induced gel‐sol‐gel transformation led to major morphological changes.
Supramolecular gels, which demonstrate tunable functionalities, have attracted much interest in a range of areas, including healthcare, environmental protection and energy-related technologies. ...Preparing these materials in a reliable manner is challenging, with an increased level of kinetic defects observed at higher self-assembly rates. Here, by combining biocatalysis and molecular self-assembly, we have shown the ability to more quickly access higher-ordered structures. By simply increasing enzyme concentration, supramolecular order expressed at molecular, nano- and micro-levels is dramatically enhanced, and, importantly, the gelator concentrations remain identical. Amphiphile molecules were prepared by attaching an aromatic moiety to a dipeptide backbone capped with a methyl ester. Their self-assembly was induced by an enzyme that hydrolysed the ester. Different enzyme concentrations altered the catalytic activity and size of the enzyme clusters, affecting their mobility. This allowed structurally diverse materials that represent local minima in the free energy landscape to be accessed based on a single gelator structure.
We demonstrate the self-assembly of bola-amphiphile-type conjugates of dipeptides and perylene bisimide (PBI) in water and other polar solvents. Depending on the nature of the peptide used ...(glycine-tyrosine, GY, or glycine-aspartic acid, GD), the balance between H-bonding and aromatic stacking can be tailored. In aqueous buffer, PBI-GY2 forms chiral nanofibers, resulting in the formation of a hydrogel, while for PBI-GD2 achiral spherical aggregates are formed, demonstrating that the peptide sequence has a profound effect on the structure formed. In water and a range of other polar solvents, self-assembly of these two PBI-peptides conjugates results in different nanostructures with highly tunable fluorescence performance depending on the peptide sequence employed, e.g., fluorescent emission and quantum yield. Organogels are formed for the PBI-GD2 derivative in DMF and DMSO while PBI-GY2 gels in DMF. To the best of our knowledge, this is the first successful strategy for using short peptides, specifically, their sequence/structure relationships, to manipulate the PBI nanostructure and consequent optical properties. The combination of controlled self-assembly, varied optical properties, and formation of aqueous and organic gel-phase materials may facilitate the design of devices for various applications related to light harvesting and sensing.
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In this work DLS, NTA, SAXS and NMR were used to investigate populations, size distributions and structure of clusters in undersaturated aqueous solutions of glycine. Molecular and ...colloidal scale (mesoscale) clusters with radii around 0.3-0.5 nm and 100–150 nm, respectively, were observed using complementary experimental techniques. Molecular clusters are consistent with hydrated glycine dimers present in equilibrium with glycine monomers in aqueous solutions. Mesoscale clusters previously observed in supersaturated glycine solutions appear to be indefinitely stable, in mutual equilibrium within mesostructured undersaturated solutions across all glycine concentrations investigated here, down to as low as 1 mg/g of water.
We report on a pronounced specific‐ion effect on the intermolecular and chiral organization, supramolecular structure formation, and resulting materials properties for a series of low molecular ...weight peptide‐based hydrogelators, observed in the presence of simple inorganic salts. This effect was demonstrated using aromatic short peptide amphiphiles, based on fluorenylmethoxycarbonyl (Fmoc). Gel‐phase materials were formed due to molecular self‐assembly, driven by a combination of hydrogen bonding and π‐stacking interactions. Pronounced morphological changes were observed by atomic force microscopy (AFM) for Fmoc‐YL peptide, ranging from dense fibrous networks to spherical aggregates, depending on the type of anions present. The gels formed had variable mechanical properties, with G′ values between 0.8 kPa and 2.4 kPa as determined by rheometry. Spectroscopic analysis provided insights into the differential mode of self‐assembly, which was found to be dictated by the hydrophobic interactions of the fluorenyl component, with comparable H‐bonding patterns observed in each case. The efficiency of the anions in promoting the hydrophobic interactions and thereby self‐assembly was found to be consistent with the Hofmeister anion sequence. Similar effects were observed with other hydrophobic peptides, Fmoc‐VL and Fmoc‐LL. The effect was found to be less pronounced for a less hydrophobic peptide, Fmoc‐AA. To get more insights into the molecular mechanism, the effect of anions on sol–gel equilibrium was investigated, which indicates the observed changes result from the specific‐ion effects on gels structure, rather than on the sol–gel equilibrium. Thus, we demonstrate that, by simply changing the ionic environment, structurally diverse materials can be accessed providing an important design consideration in nanofabrication via molecular self‐assembly.
Ions control hydrogelation: A dramatic specific‐ion effect on the intermolecular and chiral organization, supramolecular structure formation, and resulting materials properties was observed for a series of low molecular weight peptide‐based hydrogelators. Spectroscopic studies provided insights into the differential mode of self‐assembly with different ions, dictated by the hydrophobic interactions of the fluorenyl components (see figure).
Coupling of peptide self-assembly to dynamic sequence exchange provides a useful approach for the discovery of self-assembling materials. In here, we demonstrate the discovery and optimization of ...aqueous, gel-phase nanostructures based on dynamically exchanging peptide sequences that self-select to maximize charge transfer of n-type semiconducting naphthalenediimide (NDI)-dipeptide bioconjugates with various π-electron-rich donors (dialkoxy/hydroxy/amino-naphthalene or pyrene derivatives). These gel-phase peptide libraries are characterized by spectroscopy (UV–vis and fluorescence), microscopy (TEM), HPLC, and oscillatory rheology and it is found that, of the various peptide sequences explored (tyrosine Y-NDI with tyrosine Y, phenylalanine F, leucine L, valine V, alanine A or glycine G-NH2), the optimum sequence is tyrosine-phenylalanine in each case; however, both its absolute and relative yield amplification is dictated by the properties of the donor component, indicating cooperativity of peptide sequence and donor/acceptor pairs in assembly. The methodology provides an in situ discovery tool for nanostructures that enable dynamic interfacing of supramolecular electronics with aqueous (biological) systems.
We report on a supramolecular self-assembly system that displays coupled light switching, biocatalytic condensation/hydrolysis and gelation. The equilibrium state of this system can be regulated by ...light, favouring in situ formation, by protease catalysed peptide synthesis, of self-assembling trans- in ambient light; however, irradiation with UV light gives rise to the cis-isomer, which readily hydrolyzes to its amino acid derivatives (cis- + ) with consequent gel dissolution.
For the development of applications and novel uses for peptide nanostructures, robust routes for their surface functionalization, that ideally do not interfere with their self‐assembly properties, ...are required. Many existing methods rely on covalent functionalization, where building blocks are appended with functional groups, either pre‐ or post‐assembly. A facile supramolecular approach is demonstrated for the formation of functionalized nanofibers by combining the advantages of biocatalytic self‐assembly and surfactant/gelator co‐assembly. This is achieved by enzymatically triggered reconfiguration of free flowing micellar aggregates of pre‐gelators and functional surfactants to form nanofibers that incorporate and display the surfactants’ functionality at the surface. Furthermore, by varying enzyme concentration, the gel stiffness and supramolecular organization of building blocks can be varied.
A facile supramolecular approach is demonstrated for the formation of functionalized nanofibers by combining the advantages of biocatalytic self‐assembly and surfactant/gelator co‐assembly. This is achieved by enzymatically triggered reconfiguration of free flowing micellar aggregates of pre‐gelators and functional surfactants to form nanofibers that incorporate and display the surfactants’ functionality at the surface.
The effects of various kosmotropic and chaotropic cosolvents and salts on the intermolecular interaction potential of positively charged lysozyme is evaluated at varying protein concentrations by ...using synchrotron small‐angle X‐ray scattering in combination with liquid‐state theoretical approaches. The experimentally derived static structure factors S(Q) obtained without and with added cosolvents and salts are analysed with a statistical mechanical model based on the Derjaguin–Landau–Verwey–Overbeek (DLVO) potential, which accounts for repulsive and attractive interactions between the protein molecules. Different cosolvents and salts influence the interactions between protein molecules differently as a result of changes in the hydration level or solvation, in charge screening, specific adsorption of the additives at the protein surface, or increased hydrophobic interactions. Intermolecular interaction effects are significant above protein concentrations of 1 wt %, and with increasing protein concentration, the repulsive nature of the intermolecular pair potential V(r) increases markedly. Kosmotropic cosolvents like glycerol and sucrose exhibit strong concentration‐dependent effects on the interaction potential, leading to an increase of repulsive forces between the protein molecules at low to medium high osmolyte concentrations. Addition of trifluoroethanol exhibits a multiphasic effect on V(r) when changing its concentration. Salts like sodium chloride and potassium sulfate exhibit strong concentration‐dependent changes of the interaction potential due to charge screening of the positively charged protein molecules. Guanidinium chloride (GdmCl) at low concentrations exhibits a similar charge‐screening effect, resulting in increased attractive interactions between the protein molecules. At higher GdmCl concentrations, V(r) becomes more repulsive in nature due to the presence of high concentrations of Gdm+ ions binding to the protein molecules. Our findings also imply that in calculations of thermodynamic properties of proteins in solution and cosolvent mixtures, activity coefficients may not generally be neglected in the concentration range above 1 wt % protein.
Solution effects: Various kosmotropic and chaotropic cosolvents and salts are added to solutions of lysozyme, and static structure factors are determined experimentally (see picture). Statistical mechanical analysis allows for deconvolution of repulsive and attractive interactions, lending insight into protein–protein interactions on a molecular level.
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