Diphenylalanine Peptide Nanotubes Research Articles

Structure and Dynamics of Confined Water Inside Diphenylalanine Peptide Nanotubes.

Diphenylalanine (FF) peptides exhibit a unique ability to self-assemble into nanotubes with confined water molecules playing pivotal roles in their structure and function. This study investigates the structure and dynamics of diphenylalanine peptide nanotubes (FFPNTs) using all-atom molecular dynamics (MD) and grand canonical Monte Carlo combined with MD (GCMC/MD) simulations with both the CHARMM additive and Drude polarizable force fields. The occupancy and dynamics of confined water molecules were also examined. It was found that less than 2 confined water molecules per FF help stabilize the FFPNTs on the x-y plane. Analyses of the kinetics of confined water molecules revealed distinctive transport behaviors for bound and free water, and their respective diffusion coefficients were compared. Our results validate the importance of polarizable force field models in studying peptide nanotubes and provide insights into our understanding of nanoconfined water.

Molecular Dynamics Simulation of Self-Assembly Processes of Diphenylalanine Peptide Nanotubes and Determination of Their Chirality.

In this work, we further developed a new approach for modeling the processes of the self-assembly of complex molecular nanostructures using molecular dynamics methods; in particular, using a molecular dynamics manipulator. Previously, this approach was considered using the example of the self-assembly of a phenylalanine helical nanotube. Now, a new application of the algorithm has been developed for implementing a similar molecular dynamic self-assembly into helical structures of peptide nanotubes (PNTs) based on other peptide molecules-namely diphenylalanine (FF) molecules of different chirality L-FF and D-FF. In this work, helical nanotubes were assembled from linear sequences of FF molecules with these initially different chiralities. The chirality of the obtained nanotubes was calculated by various methods, including calculation by dipole moments. In addition, a statistical analysis of the results obtained was performed. A comparative analysis of the structures of nanotubes was also performed using the method of visual differential analysis. It was found that FF PNTs obtained by the MD self-assembly method form helical nanotubes of different chirality. The regimes that form nanotubes of right chirality D from initial L-FF dipeptides and nanotubes of left chirality L from D-FF dipeptides are revealed. This corresponds to the law of changing the sign of the chirality of molecular helical structures as the level of their hierarchical organization becomes more complicated.

Self-assembly of unidirectionally polarized piezoelectric peptide nanotubes using environmentally friendly solvents

Diphenylalanine (FF) peptide nanotubes are considered to be particularly promising biomaterials for bio-implantable devices due to their unique characteristics, such as strong piezoelectricity, remarkable physical properties, and chemical stability. However, the 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP)-water co-solvent system, which is often used for FF nanotube synthesis, is toxic and expensive. These are limitations for the development of eco-friendly and practical biocompatible piezoelectric devices. In this study, we developed an eco-friend and cost-effective approach for aligning piezoelectric FF nanotubes using an ethanol–water solvent system. First, we fabricated horizontally aligned FF nanotubes via a meniscus-driven self-assembly process. The fabricated FF nanotubes using ethanol exhibited unidirectional polarization and strong piezoelectric properties comparable to HFIP solvent based FF nanotubes. In addition, the FF-based piezoelectric nanogenerator generates voltage, current, and power of up to 1.66 V, 19.4 nA, and 19.2 nW, respectively, with a force of 40 N. These FF-based piezoelectric nanogenerators will be applicable as a compatible energy source for future biomedical applications.

Structural Transition-Induced Raman Enhancement in Bioinspired Diphenylalanine Peptide Nanotubes.

Semiconducting materials are increasingly proposed as alternatives to noble metal nanomaterials to enhance Raman scattering. We demonstrate that bioinspired semiconducting diphenylalanine peptide nanotubes annealed through a reported structural transition can support Raman detection of 10–7 M concentrations for a range of molecules including mononucleotides. The enhancement is attributed to the introduction of electronic states below the conduction band that facilitate charge transfer to the analyte molecule. These results show that organic semiconductor-based materials can serve as platforms for enhanced Raman scattering for chemical sensing. As the sensor is metal-free, the enhancement is achieved without the introduction of electromagnetic surface-enhanced Raman spectroscopy.

Modeling and physical properties of diphenylalanine peptide nanotubes containing water molecules

DFT (VASP) and semi-empirical (HyperChem) calculations for the D-chiral diphenylalanine (D-FF) peptide nanotube (PNT) structures, empty and filled with water/ice clusters, are presented and analyzed. The obtained results show that after the optimization the dipole moment and polarization of both D-FF PNT and embedded water/ice cluster are enhanced; the water/ice cluster acquires a helix-like structure similar to that of D-FF PNT. Possible ferroelectric properties of the tubular water/ice helix-like cluster inside the D-FF PNT are discussed.

Molecular modeling and computational study of the chiral-dependent structures and properties of the self-assembling diphenylalanine peptide nanotubes, containing water molecules.

DFT (VASP) and semi-empirical (HyperChem) calculations for the L- and D-chiral diphenylalanine (L-FF and D-FF) nanotube (PNT) structures, empty and filled with water/ice clusters, are presented and analyzed. The results obtained show that after optimization, the dipole moment and polarization of both chiral type L-FF and D-FF PNT and embedded water/ice cluster are enhanced; the water/ice cluster acquire the helix-like structure similar as L-FF and D-FF PNT. Ferroelectric properties of tubular water/ice helix-like-cluster obtained after optimization inside L-FF and D-FF PNT and total L-FF and D-FF PNT with embedded water/ice cluster are discussed.

Structures and Properties of the Self-Assembling Diphenylalanine Peptide Nanotubes Containing Water Molecules: Modeling and Data Analysis.

The structures and properties of the diphenylalanine (FF) peptide nanotubes (PNTs), both L-chiral and D-chiral (L-FF and D-FF) and empty and filled with water/ice clusters, are presented and analyzed. DFT (VASP) and semi-empirical calculations (HyperChem) to study these structural and physical properties of PNTs (including ferroelectric) were used. The results obtained show that after optimization the dipole moment and polarization of both chiral type L-FF and D-FF PNT and embedded water/ice cluster are enhanced; the water/ice cluster acquire the helix-like structure similar as L-FF and D-FF PNT. Ferroelectric properties of tubular water/ice helix-like cluster, obtained after optimization inside L-FF and D-FF PNT, as well of the total L-FF and D-FF PNT with embedded water/ice cluster, are discussed.

Energy harvesting with peptide nanotube–graphene oxide flexible substrates prepared with electric field and wettability assisted self-assembly

Piezoelectric diphenylalanine peptide nanotubes (PNTs) have recently been demonstrated in energy harvesting applications, typically based on vertically aligned PNTs that generate charge when pressed. In this work, we use a wettability difference and an applied electric field to align PNTs and PNT-based composites on flexible substrates. Open-circuit voltages and short-circuit currents exceeding 6 V and 60 nA, respectively, are achieved by bending the substrate, opening up the use of horizontally aligned PNTs as flexible energy harvesting substrates.

Sonochemical Functionalization of Cotton and Non‐Woven Fabrics with Bio‐Inspired Self‐Assembled Nanostructures

AbstractCotton and non‐woven fabrics are commonly used for medical applications such as wound dressing. In recent years, there has been a growing interest in developing functionalized fabrics that allow the sustained release of active molecules for large‐scale production. However, several limitations of currently used technologies restrict the ability to form durable fabrics with functional coatings. Herein, using a sonochemical process, we successfully deposited diphenylalanine (FF) peptide nanotubes on cotton and non‐woven fabrics. FF peptide nanotubes were loaded with curcumin, an antimicrobial and anti‐inflammatory agent. The structure of the fabric decorated with nanotubes was studied by electron microscopy, and the sustained release of curcumin was demonstrated using absorbance measurements. Sonication duration was positively correlated with the deposition of the nanotubes onto the fabrics’ fibers as well as the retention of the curcumin within the FF nanotubes. These results suggest that the sonochemical process may be used for large‐scale fabrication of functionalized commercial fabrics.

Molecular modeling and computational study of the chiral-dependent structures and properties of self-assembling diphenylalanine peptide nanotubes.

The structure and properties of diphenylalanine (FF) peptide nanotubes (PNT) based on phenylalanine were investigated by various molecular modeling methods. The main approach employed semi-empirical quantum-chemical methods (PM3 and AM1). Ab initio, density functional theory methods and molecular mechanical approaches were also used. Both model structures and structures extracted from experimental crystallographic databases obtained by X-ray methods were examined. A comparison of optimized model structures and structures obtained by natural self-assembly revealed important differences depending on chirality: D and L. In both the cases, the effect of chirality on the results of self-assembly of FF PNT was established: PNT based on the D-FF has large condensation energy E0 in the transverse direction, and form thicker and shorter PNT bundles than those based on L-FF. A topological difference was established: model PNT were optimized into structures consisting of rings, while naturally self-assembled PNT consisted of helical turns. The latter nanotubes differed from the original L-FF and D-FF and formed helix structures of different chirality signs in accordance with the alternation rule of chirality due to macromolecule hierarchy. A topological transition between ring and helix turn PNT structures is discussed: self-assembled natural helix structures are favorable and their energy is lower by a value of the order of one to several eV.

Chiral Peculiar Properties of Self-Organization of Diphenylalanine Peptide Nanotubes: Modeling Of Structure and Properties

The structure and properties of diphenylalanine peptide nanotubes based on phenylalanine were investigated by various molecular modeling methods. The main approaches were semi-empirical quantum-chemical methods (PM3 and AM1), and molecular mechanical ones. Both the model structures and the structures extracted from their experimental crystallographic databases obtained by X-ray methods were examined. A comparison of optimized model structures and structures obtained by naturally-occurring self-assembly showed their important differences depending on D- and L-chirality. In both the cases, the effect of chirality on the results of self-assembly of diphenylalanine peptide nanotubes was established: peptide nanotubes based on the D-diphenylalanine (D-FF) has high condensation energy E0 in transverse direction and forms thicker and shorter peptide nanotubes bundles, than that based on L-diphenylalanine (L-FF). A topological difference was established: model peptide nanotubes were optimized into structures consisting of rings, while naturally self-assembled peptide nanotubes consisted of helical coils. The latter were different for the original L-FF and D-FF. They formed helix structures in which the chirality sign changes as the level of the macromolecule hierarchy raises. Total energy of the optimal distances between two units are deeper for L-FF (–1.014 eV) then for D-FF (–0.607 eV) for ring models, while for helix coil are approximately the same and have for L-FF (–6.18 eV) and for D-FF (–6.22 eV) by PM3 method; for molecular mechanical methods energy changes are of the order of 2–3 eV for both the cases. A topological transition between a ring and a helix coil of peptide nanotube structures is discussed: self-assembled natural helix structures are more stable and favourable, they have lower energy in optimal configuration as compared with ring models by a value of the order of 1 eV for molecular mechanical methods and 5 eV for PM3 method.

Self-assembling diphenylalanine peptide nanotubes selectively eradicate bacterial biofilm infection

Biofilms present a major problem to industry and healthcare worldwide. Composed of a population of surface-attached microbial cells surrounded by a protective extracellular polysaccharide matrix, they are responsible for increased tolerance to antibiotics, treatment failure and a resulting rise in antimicrobial resistance. Here we demonstrate that self-assembled peptide nanostructures composed of a diphenylalanine motif provide sufficient antibacterial activity to eradicate mature biofilm forms of bacteria widely implicated in hospital infections. Modification of terminal functional groups to amino (–NH2), carboxylic acid (–COOH) or both modalities, and switch to d-isomers, resulted in changes in antibacterial selectivity and mammalian cell toxicity profiles. Of the three peptide nanotubes structures studied (NH2-FF-COOH, NH2-ff-COOH and NH2-FF-NH2), NH2-FF-COOH demonstrated the most potent activity against both planktonic (liquid, free-floating) and biofilm forms of bacteria, possessing minimal mammalian cell toxicity. NH2-FF-COOH resulted in greater than 3 Log10 CFU/mL viable biofilm reduction (>99.9%) at 5 mg/mL and total biofilm kill at 10 mg/mL against Staphylococcus aureus after 24 h exposure. Scanning electron microscopy proved that antibiofilm activity was primarily due to the formation of ion channels and/or surfactant-like action, with NH2-FF-COOH and NH2-ff-COOH capable of degrading the biofilm matrix and disrupting cell membranes, leading to cell death in Gram-positive bacterial isolates. Peptide-based nanotubes are an exciting platform for drug delivery and engineering applications. This is the first report of using peptide nanotubes to eradicate bacterial biofilms and provides evidence of a new platform that may alleviate their negative impact throughout society. Statement of SignificanceWe outline, for the first time, the antibiofilm activity of diphenylalanine (FF) peptide nanotubes. Biofilm bacteria exhibit high tolerance to antimicrobials 10–10,000 times that of free-flowing planktonic forms. Biofilm infections are difficult to treat using conventional antimicrobial agents, leading to a rise in antimicrobial resistance. We discovered nanotubes composed of NH2-FF-COOH demonstrated potent activity against staphylococcal biofilms implicated in hospital infections, resulting in complete kill at concentrations of 10 mg/mL. Carboxylic acid terminated FF nanotubes were able to destroy the exopolysaccharide architecture of staphylococcal biofilms expressing minimal toxicity, highlighting their potential for use in patients. Amidated (NH2-FF-NH2) forms demonstrated reduced antibiofilm efficacy and significant toxicity. These results contribute significantly to the development of innovative antibacterial technologies and peptide nanomaterials.

Effect of the Chloride Anions on the Formation of Self-Assembled Diphenylalanine Peptide Nanotubes.

Self-assembled peptide nanostructures are being intensively investigated due to their potential applications such as biosensors, piezotransducers, and microactuators. It was predicted that their formation and hence piezoelectric property strongly depend on the water content and acidity of the stock solution. In this paper, simple diphenylalanine (FF) tubular structures were fabricated from the solutions with added hydrochloric acid in order to understand the influence of chloride ions on the self-assembly process and resulting piezoelectricity. Low-frequency Raman scattering, atomic, and piezoresponse force microscopies were used to characterize both the morphology and piezoelectric properties of the grown samples. The mechanism of chloride anions' effect on the formation of self-assembled peptide nanostructures is discussed based on the acquired Raman data and quantum-chemical modeling. It is shown that the addition of chloride anions causes a significant reduction of the dipole moments of FF tubes accompanied with the concomitant decrease of tube dimensions and apparent shear piezoelectric coefficients.

Vertical Alignment of Size-Controlled Self-Assembled Diphenylalanine Peptide Nanotubes Using Polyethersulfone Hollow Fiber Membranes On Silicon

The strong piezoelectricity in diphenylalanine peptide develops its technological potential as a smart material. To achieve insight into the vertical alignment of size-controlled self-assembled diphenylalanine peptide nanotubes, an aromatic peptide of diphenylalanine (FF) was applied in this research as the model peptide. Here we found for the first time a vertical alignment of size-controlled self-assembled diphenylalanine peptide nanotubes during the peptide self-assembly process of nanotubes composite using polyethersulfone (PES) membrane in situ and ex situ peregnation of peptide nano tube. The membrane structure was investigated using fluofenamic acid as a fluorescent tag and a first-line solution containing dipeptides and hexafluoropropane (HFP). The results showed a vertical alignment of size-controlled self-assembled diphenylalanine peptide nanotubes formation on silicon. The STM and SEM results indicated the formation of different nanostructures including short nanorods, nanotubes branched nanotubes and dendritic nanostructures of peptide in PES membrane. Our novel approach based on the PES membrane and HFP allows one to controllably fabricate various peptide-based nanostructures on silicon.

Investigation of physical properties of diphenylalanine peptide nanotubes having different chiralities and embedded water molecules

ABSTRACTMolecular modeling of diphenylalanine peptide nanotubes (FF PNT) is performed using PM3 method in HyperChem. The study focuses on the polar properties of FF PNT structures having different chiralities (L, D) and conformations (α-helix, β-sheet). The results show that the optimized structures for L-PNT possess higher polarization in both conformations (0.023 C/m2 – α, 0.04 C/m2 – β) compared with D-PNT (0.016 C/m2 – α, 0.014 C/m2 – β). The water structures inside PNT are investigated, too. The hexagonal ice/water structures used for these models are analyzed in respect to the XRD data recently obtained.

Photo-induced surface-enhanced Raman spectroscopy from a diphenylalanine peptide nanotube-metal nanoparticle template

UV irradiation of aligned diphenylalanine peptide nanotubes (FF-PNTs) decorated with plasmonic silver nanoparticles (Ag NPs) enables photo-induced surface-enhanced Raman spectroscopy. UV-induced charge transfer facilitates a chemical enhancement that provides up to a 10-fold increase in surface-enhanced Raman intensity and allows the detection of a wide range of small molecules and low Raman cross-section molecules at concentrations as low as 10–13 M. The aligned FF-PNT/Ag NP template further prevents photodegradation of the molecules under investigation. Our results demonstrate that FF-PNTs can be used as an alternative material to semiconductors such as titanium dioxide for photo-induced surface-enhanced Raman spectroscopy applications.

An atomic force microscopy mode for nondestructive electromechanical studies and its application to diphenylalanine peptide nanotubes

Nondestructive scanning probe microscopy of fragile nanoscale objects is currently in increasing need. In this paper, we report a novel atomic force microscopy mode, HybriD Piezoresponse Force Microscopy (HD-PFM), for simultaneous nondestructive analysis of piezoresponse as well as of mechanical and dielectric properties of nanoscale objects. We demonstrate this mode in application to self-assembled diphenylalanine peptide micro- and nanotubes formed on a gold-covered substrate. Nondestructive in- and out-of-plane piezoresponse measurements of tubes of less than 100 nm in diameter are demonstrated for the first time. High-resolution maps of tube elastic properties were obtained simultaneously with HD-PFM. Analysis of the measurement data combined with the finite-elements simulations allowed quantification of tube Young's modulus. The obtained value of 29 ± 1 GPa agrees well with the data obtained with other methods and reported in the literature.

Hybrid mode piezoresponse force microscopy for compositional electromechanical study of biopiezoelectrics

We present our recent development of new approach for compositional study of topography, nanomechanical and piezoelectric properties with nanometer spatial resolution and demonstrate it in application to two types of biopiezoelectrics: type I collagen and diphenylalanine peptide nanotubes.

Patterning protein conjugates into organized microarrays with diphenylalanine peptide nanotubes self-assembled on graphite and gold electrode

Controlling the arrangement and organization of self-assembled peptide nanostructures is a crucial step in developing Lab-on-a-Chip devices based on biomolecular assembly. Here, we report a simple approach to achieve the vertically aligned assembly of diphenylalanine (FF) peptide by casting stock solution of FF peptide on gold and graphite modified silicones. We show at the first time the formation of highly ordered interlaced arrays of vertical flower crystals and peptide nanotubes (PNTs) on thiolated gold and graphite. Furthermore, their chemical stability was investigated in PBS buffer after 3 h to gain insight into the stability of modified electrodes upon cycling. Interestingly, a highly ordered hierarchical morphology was obtained on the substrate surface. Hierarchical morphology resembles a square lattice, dendritic forest, and three-dimensional packed arrays. The results confirmed that PNTs not only preserves its chemical stability but transform into hierarchical arrays in PBS which is very beneficial for their applications in bioelectrochemical and nanoelectronics devices. As an example, the significantly enhanced arrangement of antibody CD3 was also demonstrated at the PNTs modified gold electrode compared to unordered modified electrodes. The simple and mild approach described here opens a new path for the fabrication of organized self-assembled peptide bionanostructure arrays allowing the fabrication of a variety of microarrays used in practical applications.

Peptide Optical waveguides.

Small-scale optical devices, designed and fabricated onto one dielectric substrate, create integrated optical chip like their microelectronic analogues. These photonic circuits, based on diverse physical phenomena such as light-matter interaction, propagation of electromagnetic waves in a thin dielectric material, nonlinear and electro-optical effects, allow transmission, distribution, modulation, and processing of optical signals in optical communication systems, chemical and biological sensors, and more. The key component of these optical circuits providing both optical processing and photonic interconnections is light waveguides. Optical confinement and transmitting of the optical waves inside the waveguide material are possible due to the higher refractive index of the waveguides in comparison with their surroundings. In this work, we propose a novel field of bionanophotonics based on a new concept of optical waveguiding in synthetic elongated peptide nanostructures composed of ordered peptide dipole biomolecules. New technology of controllable deposition of peptide optical waveguiding structures by nanofountain pen technique is developed. Experimental studies of refractive index, optical transparency, and linear and nonlinear waveguiding in out-of-plane and in-plane diphenylalanine peptide nanotubes have been conducted. Optical waveguiding phenomena in peptide structures are simulated by the finite difference time domain method. The advantages of this new class of bio-optical waveguides are high refractive index contrast, wide spectral range of optical transparency, large optical nonlinearity, and electro-optical effect, making them promising for new applications in integrated multifunctional photonic circuits. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.