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Despite extensive research on the nucleation and growth of calcium oxalate (CaOx) crystals, there are still several challenges and unknowns that remain. In particular, the role of trace metal elements in the promotion or inhibition of CaOx crystals is not well understood. In the present study, in situ graphene liquid cell transmission electron microscopy (in situ GLC TEM) was used to observe real-time, nanoscale transformations of CaOx crystals in the presence of nickel ions (Ni2+). The results showed that Ni2+ form Ni-water complexes, acting as a shape-directing species, generating a unique morphology and altering growth kinetics. Transient adsorption of Ni-water complexes resulted in a metastable phase formation of calcium oxalate trihydrate. Atomistic molecular dynamics simulations confirmed that Ni2+ acts as a weak inhibitor which slows down the CaOx crystallization, elucidating that Ni2+ impacts small-sized CaOx clusters by bringing more water into the clusters. This work highlighted the intricacies behind the effect of Ni2+ on CaOx biomineralization that were made possible to discern using in situ GLC TEM.
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Self-assembled peptide fibrils have been used extensively to template the organization of metal nanoparticles in a one-dimensional (1D) array. It has been observed that the formation of the 1D arrays with a width of a single or few nanoparticles (viz. 20 nm diameter) is only possible if the templating fibers have comparable diameters (viz. ≤20 nm). Accordingly, until today, all the peptide-based templates enabling such 1D arrays have very low persistence lengths, a property that depends strongly on the diameter of the template, owing to the inherent flexibility of only a few nanometer-wide fibers. Here, we demonstrate the formation of high persistence length 1D arrays templated by a short self-assembling peptide fibril with an asymmetrically distributed charged surface. The asymmetric nature of the peptide fibril allows charge-dependent deposition of the nanoparticles only to the part of the fiber with complementary charges, and the rest of the fibril surface remains free of nanoparticles. Consequently, fibers with a much higher diameter, which will have a higher persistence length, are able to template single or few nanoparticle-wide 1D arrays. Detailed microscopy, molecular dynamics simulations, and crystal structure analysis provide molecular-level insights into fiber asymmetry and its interactions with diverse nanostructures such as gold and magnetic nanoparticles. This study will afford an alternative paradigm for high persistence length 1D array fabrication comparable to DNA nanotechnology and lithography but with tremendous cost-effectiveness.
Assuntos
Nanopartículas Metálicas , Nanofibras , Nanoestruturas , Propriedades de Superfície , Ouro/química , Nanoestruturas/química , Nanopartículas Metálicas/química , Peptídeos/químicaRESUMO
The multivalent binding effect has been the subject of extensive studies to modulate adhesion behaviors of various biological and engineered systems. However, precise control over the strong avidity-based binding remains a significant challenge. Here, a set of engineering strategies are developed and tested to systematically enhance the multivalent binding of peptides in a stepwise manner. Poly(amidoamine) (PAMAM) dendrimers are employed to increase local peptide densities on a substrate, resulting in hierarchically multivalent architectures (HMAs) that display multivalent dendrimer-peptide conjugates (DPCs) with various configurations. To control binding behaviors, effects of the three major components of the HMAs are investigated: i) poly(ethylene glycol) (PEG) linkers as spacers between conjugated peptides; ii) multiple peptides on the DPCs; and iii) various surface arrangements of HMAs (i.e., a mixture of DPCs each containing different peptides vs DPCs cofunctionalized with multiple peptides). The optimized HMA configuration enables significantly enhanced target cell binding with high selectivity compared to the control surfaces directly conjugated with peptides. The engineering approaches presented herein can be applied individually or in combination, providing guidelines for the effective utilization of biomolecular multivalent interactions using DPC-based HMAs.
Assuntos
Neoplasias da Mama/metabolismo , Adesão Celular , Nanopartículas/metabolismo , Peptídeos/metabolismo , Linhagem Celular Tumoral , Dendrímeros/metabolismo , Humanos , Fenômenos Físicos , Polietilenoglicóis/metabolismoRESUMO
In cellular environments, metabolites, peptides, proteins, and other biomolecules can self-assemble into planar and fibrilar molecular crystals. We use atomistic molecular dynamics simulations to show that such biomolecular crystals coupled with low-dimensional materials can form stable hybrid superstructures. We discuss enantiopure and racemic TRP and PHE amino acid crystals adsorbed on or intercalated between graphene, phosphorene, and carbon nanotubes. While racemic biomolecular crystals tend to stay straight in solutions and when adsorbed on flat and cylindrical nanosurfaces, enantiopure crystals undergo twisting. Mixed material properties of these hybrid superstructures can be attractive in many applications.
Assuntos
Grafite , Nanotubos de Carbono , Aminoácidos , Simulação de Dinâmica Molecular , PeptídeosRESUMO
Bacterial type IV pili (T4P) are polymeric protein nanofibers that have diverse biological roles. Their unique physicochemical properties mark them as a candidate biomaterial for various applications, yet difficulties in producing native T4P hinder their utilization. Recent effort to mimic the T4P of the metal-reducing Geobacter sulfurreducens bacterium led to the design of synthetic peptide building blocks, which self-assemble into T4P-like nanofibers. Here, it is reported that the T4P-like peptide nanofibers efficiently bind metal oxide particles and reduce Au ions analogously to their native counterparts, and thus give rise to versatile and multifunctional peptide-metal nanocomposites. Focusing on the interaction with Au ions, a combination of experimental and computational methods provides mechanistic insight into the formation of an exceptionally dense Au nanoparticle (AuNP) decoration of the nanofibers. Characterization of the thus-formed peptide-AuNPs nanocomposite reveals enhanced thermal stability, electrical conductivity from the single-fiber level up, and substrate-selective adhesion. Exploring its potential applications, it is demonstrated that the peptide-AuNPs nanocomposite can act as a reusable catalytic coating or form self-supporting immersible films of desired shapes. The films scaffold the assembly of cardiac cells into synchronized patches, and present static charge detection capabilities at the macroscale. The study presents a novel T4P-inspired biometallic material.
Assuntos
Nanopartículas Metálicas/química , Nanocompostos/química , Nanofibras/química , Peptídeos/química , Materiais Biocompatíveis/química , Condutividade Elétrica , Fímbrias Bacterianas , GeobacterRESUMO
The ensemble of native, folded state was once considered to represent the global energy minimum of a given protein sequence. More recently, the discovery of the cross-ß amyloid state revealed that deeper energy minima exist, often associated with pathogenic, fibrillar deposits, when the concentration of proteins reaches a critical value. Fortunately, a sizable energy barrier impedes the conversion from native to pathogenic states. However, little is known about the structure of the related transition state. In addition, there are indications of polymorphism in the amyloidogenic process. Here, we report the first evidence of the conversion of metastable cross-α-helical crystals to thermodynamically stable cross-ß-sheet-like fibrils by a de novo designed heptapeptide. Furthermore, for the first time, we demonstrate at atomic resolution that the flip of a peptide plane from a type I to a type II' turn facilitates transformation to cross-ß structure and assembly of a dry steric zipper. This study establishes the potential of a peptide turn, a common protein secondary structure, to serve as a principal gatekeeper between a native metastable folded state and the amyloid state.
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Amiloide/química , Agregados Proteicos , Cinética , Modelos Moleculares , Peptídeos/química , Dobramento de Proteína , Estrutura Secundária de Proteína , TermodinâmicaRESUMO
Conspectus Molecular mechanical force fields have been successfully used to model condensed-phase and biological systems for a half century. By means of careful parametrization, such classical force fields can be used to provide useful interpretations of experimental findings and predictions of certain properties. Yet, there is a need to further improve computational accuracy for the quantitative prediction of biomolecular interactions and to model properties that depend on the wave functions and not just the energy terms. A new strategy called explicit polarization (X-Pol) has been developed to construct the potential energy surface and wave functions for macromolecular and liquid-phase simulations on the basis of quantum mechanics rather than only using quantum mechanical results to fit analytic force fields. In this spirit, this approach is called a quantum mechanical force field (QMFF). X-Pol is a general fragment method for electronic structure calculations based on the partition of a condensed-phase or macromolecular system into subsystems ("fragments") to achieve computational efficiency. Here, intrafragment energy and the mutual electronic polarization of interfragment interactions are treated explicitly using quantum mechanics. X-Pol can be used as a general, multilevel electronic structure model for macromolecular systems, and it can also serve as a new-generation force field. As a quantum chemical model, a variational many-body (VMB) expansion approach is used to systematically improve interfragment interactions, including exchange repulsion, charge delocalization, dispersion, and other correlation energies. As a quantum mechanical force field, these energy terms are approximated by empirical functions in the spirit of conventional molecular mechanics. This Account first reviews the formulation of X-Pol, in the full variationally correct version, in the faster embedded version, and with systematic many-body improvements. We discuss illustrative examples involving water clusters (which show the power of two-body corrections), ethylmethylimidazolium acetate ionic liquids (which reveal that the amount of charge transfer between anion and cation is much smaller than what has been assumed in some classical simulations), and a solvated protein in aqueous solution (which shows that the average charge distribution of carbonyl groups along the polypeptide chain depends strongly on their position in the sequence, whereas they are fixed in most classical force fields). The development of QMFFs also offers an opportunity to extend the accuracy of biochemical simulations to areas where classical force fields are often insufficient, especially in the areas of spectroscopy, reactivity, and enzyme catalysis.
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Modelos Químicos , Teoria Quântica , Água/química , Líquidos Iônicos/química , Simulação de Dinâmica Molecular , Proteínas/química , Eletricidade Estática , TemperaturaRESUMO
A study of the x-ray sensitivity of amorphous selenium (a-Se) for digital mammography has been performed. A uniform layer of a-Se was deposited on a glass substrate with electrodes on both surfaces. The deposition procedure was identical to that used for a-Se flat-panel detectors. A high voltage was applied to the top surface of the a-Se layer in order to establish an electric field E(Se). Then the sample was exposed to x rays with 27 kVp spectra generated from an x-ray tube with a molybdenum (Mo) target. The mean x-ray energy of the spectrum used was approximately 16.6 keV. The x-ray current generated by the a-Se layer was measured as a function of E(Se). From the current measurement and the estimation of total x-ray energy absorbed in the a-Se, the energy required to create one electron-hole pair (EHP), W, was determined as a function of E(Se). It was found that at the most commonly used E(Se) of 10 V/microm, W was measured as 64 eV. This is considerably higher than the widely accepted typical value of W = 50 eV measured at higher x-ray photon energies (e.g., 50 keV). The dependence of W as a function of E(Se) can be best fitted using the empirical expression of E(Se)-gamma. This relationship is consistent with the results obtained at higher x-ray energies. This article provides an accurate measurement of x-ray sensitivity of a-Se at mammographic energies independent of detector operation, such as the most recently developed flat-panel detectors. The results will be a useful tool for investigation and optimization of a-Se-based x-ray imaging detectors, such as determination of pixel fill-factor and optimal E(Se) during operation.