Search

Peptide-based self-assembly has been used to produce a wide range of nanostructures. While most of these systems involve self-assembly of α-peptides, more recently β-peptides have also been shown to undergo supramolecular self-assembly, and have been used to produce materials for applications in tissue engineering, cell culture and drug delivery. In order to engineer new materials with specific structure and function, theoretical molecular modelling can provide significant insights into the collective balance of non-covalent interactions that drive the self-assembly and determine the structure of the resultant supramolecular materials under different conditions. However, this approach has only recently become feasible for peptide-based self-assembled nanomaterials, particularly those that incorporate non α-amino acids. This perspective provides an overview of the challenges associated with computational modelling of the self-assembly of β-peptides and the recent success using a combination of experimental and computational techniques to provide insights into the self-assembly mechanisms and fully atomistic models of these new biocompatible materials., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Human amylin is an inherently disordered protein whose ability to form amyloid fibrils is linked to the onset of type II diabetes. Graphitic nanomaterials have potential in managing amyloid diseases as they can disrupt protein aggregation processes in biological settings, but optimising these materials to prevent fibrillation is challenging. Here, we employ bias-exchange molecular dynamics simulations to systematically study the structure and adsorption preferences of amylin on graphitic nanoflakes that vary in their physical dimensions and surface functionalisation. Our findings reveal that nanoflake size and surface oxidation both influence the structure and adsorption preferences of amylin. The purely hydrophobic substrate of pristine graphene (PG) nanoflakes encourages non-specific protein adsorption, leading to unrestricted lateral mobility once amylin adheres to the surface. Particularly on larger PG nanoflakes, this induces structural changes in amylin that may promote fibril formation, such as the loss of native helical content and an increase in β-sheet character. In contrast, oxidised graphene nanoflakes form hydrogen bonds between surface oxygen sites and amylin, and as such restricting protein mobility. Reduced graphene oxide (rGO) flakes, featuring lower amounts of surface oxidation, are amphiphilic and exhibit substantial regions of bare carbon which promote protein binding and reduced conformational flexibility, leading to conservation of the native structure of amylin. In comparison, graphene oxide (GO) nanoflakes, which are predominantly hydrophilic and have a high degree of surface oxidation, facilitate considerable protein structural variability, resulting in substantial contact area between the protein and GO, and subsequent protein unfolding. Our results indicate that tailoring the size, oxygen concentration and surface patterning of graphitic nanoflakes can lead to specific and robust protein binding, ultimately influencing the likelihood of fibril formation. These atomistic insights provide key design considerations for the development of graphitic nanoflakes that can modulate protein aggregation by sequestering protein monomers in the biological environment and inhibit conformational changes linked to amyloid fibril formation.

β-Peptides have great potential as novel biomaterials and therapeutic agents, due to their unique ability to self-assemble into low dimensional nanostructures, and their resistance to enzymatic degradation in vivo. However, the self-assembly mechanisms of β-peptides, which possess increased flexibility due to the extra backbone methylene groups present within the constituent β-amino acids, are not well understood due to inherent difficulties of observing their bottom-up growth pathway experimentally. A computational approach is presented for the bottom-up modelling of the self-assembled lipidated β 3 -peptides, from monomers, to oligomers, to supramolecular low-dimensional nanostructures, in all-atom detail. The approach is applied to elucidate the self-assembly mechanisms of recently discovered, distinct structural morphologies of low dimensional nanomaterials, assembled from lipidated β 3 -peptide monomers. The resultant structures of the nanobelts and the twisted fibrils are stable throughout subsequent unrestrained all-atom molecular dynamics simulations, and these assemblies display good agreement with the structural features obtained from X-ray fiber diffraction and atomic force microscopy data. This is the first reported, fully-atomistic model of a lipidated β 3 -peptide-based nanomaterial, and the computational approach developed here, in combination with experimental fiber diffraction analysis and atomic force microscopy, will be useful in elucidating the atomic scale structure of self-assembled peptide-based and other supramolecular nanomaterials., (© 2024 The Authors. Advanced Materials published by Wiley‐VCH GmbH.)

Metal-phenolic networks (MPNs) have received widespread interest owing to their modular incorporation of functional metal ions and phenolic ligands. However, the interaction between MPNs and biomolecules is still relatively unexplored. Herein, we studied the effects of MPN-coated gold nanoparticles on amyloid fibril formation (which is associated with Alzheimer's disease) as a function of the metal ion in the MPN systems. All coated particles examined inhibited amyloid formation, with cobalt(ii) MPN-coated particles exhibiting the highest inhibition activity (90%). Molecular dynamics simulations and quantum mechanics calculations suggested that the geometry of the exposed cobalt coordination site in the cobalt-tannic acid networks facilitates its interactions with histidine and methionine residues in the amyloid beta peptides. Furthermore, the unique structure of cobalt MPNs may enable a wider variety of biomedical applications.

Nanostructured materials have potential as platforms for analytical assays and catalytic reactions. Herein, we report the synthesis of electrocatalytically active cobalt phosphate nanostructures (CPNs) using a simple, low-cost, and scalable preparation method. The electrocatalytic properties of CPNs toward the electrooxidation of glucose (Glu) were studied by cyclic voltammetry and chronoamperometry in relevant biological electrolytes, such as phosphate-buffered saline (PBS), at physiological pH (7.4). Using CPNs, Glu detection could be achieved over a wide range of biologically relevant concentrations, from 1 to 30 mM Glu in PBS, with a sensitivity of 7.90 nA/mM cm 2 and a limit of detection of 0.3 mM, thus fulfilling the necessary requirements for human blood Glu detection. In addition, CPNs showed a high structural and functional stability over time at physiological pH. The CPN-coated electrodes could also be used for Glu detection in the presence of interfering agents (e.g., ascorbic acid and dopamine) and in human serum. Density functional theory calculations were performed to evaluate the interaction of Glu with different faceted cobalt phosphate surfaces; the results revealed that specific surface presentations of under-coordinated cobalt led to the strongest interaction with Glu, suggesting that enhanced detection of Glu by CPNs can be achieved by lowering the surface coordination of cobalt. Our results highlight the potential use of phosphate-based nanostructures as catalysts for electrochemical sensing of biochemical analytes.

Experimental studies have demonstrated that nanoparticles can affect the rate of protein self-assembly, possibly interfering with the development of protein misfolding diseases such as Alzheimer's, Parkinson's and prion disease caused by aggregation and fibril formation of amyloid-prone proteins. We employ classical molecular dynamics simulations and large-scale density functional theory calculations to investigate the effects of nanomaterials on the structure, dynamics and binding of an amyloidogenic peptide apoC-II(60-70). We show that the binding affinity of this peptide to carbonaceous nanomaterials such as C60, nanotubes and graphene decreases with increasing nanoparticle curvature. Strong binding is facilitated by the large contact area available for π-stacking between the aromatic residues of the peptide and the extended surfaces of graphene and the nanotube. The highly curved fullerene surface exhibits reduced efficiency for π-stacking but promotes increased peptide dynamics. We postulate that the increase in conformational dynamics of the amyloid peptide can be unfavorable for the formation of fibril competent structures. In contrast, extended fibril forming peptide conformations are promoted by the nanotube and graphene surfaces which can provide a template for fibril-growth.

Interfacial modular assembly has emerged as an adaptable strategy for engineering the surface properties of substrates in biomedicine, photonics, and catalysis. Herein, we report a versatile and robust coating (pBDT‐TA), self‐assembled from tannic acid (TA) and a self‐polymerizing aromatic dithiol (i.e., benzene‐1,4‐dithiol, BDT), that can be engineered on diverse substrates with a precisely tuned thickness (5–40 nm) by varying the concentration of BDT used. The pBDT‐TA coating is stabilized by covalent (disulfide) bonds and supramolecular (π‐π) interactions, endowing the coating with high stability in various harsh aqueous environments across ionic strength, pH, temperature (e.g., 100 mM NaCl, HCl (pH 1) or NaOH (pH 13), and water at 100 °C), as well as surfactant solution (e.g., 100 mM Triton X‐100) and biological buffer (e.g., Dulbecco's phosphate‐buffered saline), as validated by experiments and simulations. Moreover, the reported pBDT‐TA coating enables secondary reactions on the coating for engineering hybrid adlayers (e.g., ZIF‐8 shells) via phenolic‐mediated adhesion, and the facile integration of aromatic fluorescent dyes (e.g., rhodamine B) via π interactions without requiring elaborate synthetic processes. [ABSTRACT FROM AUTHOR]