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1. Molecular complementarity and structural heterogeneity within co-assembled peptide β-sheet nanofibers

   https://doi.org/10.1039/c9nr08725g  

   Wong, Kong M. ; Wang, Yiming ; Seroski, Dillon T. ; Larkin, Grant E. ; Mehta, Anil K. ; Hudalla, Gregory A. ; Hall, Carol K. ; Paravastu, Anant K. ( February 2020 , Nanoscale)

   null (Ed.)

   Self-assembling peptides have garnered an increasing amount of interest as a functional biomaterial for medical and biotechnological applications. Recently, β-sheet peptide designs utilizing complementary pairs of peptides composed of charged amino acids positioned to impart co-assembly behavior have expanded the portfolio of peptide aggregate structures. Structural characterization of these charge-complementary peptide co-assemblies has been limited. Thus, it is not known how the complementary peptides organize on the molecular level. Through a combination of solid-state NMR measurements and discontinuous molecular dynamics simulations, we investigate the molecular organization of King–Webb peptide nanofibers. KW+ and KW− peptides co-assemble into near stoichiometric two-component β-sheet structures as observed by computational simulations and 13 C– 13 C dipolar couplings. A majority of β-strands are aligned with antiparallel nearest neighbors within the β-sheet as previously suggested by Fourier transform infrared spectroscopy measurements. Surprisingly, however, a significant proportion of β-strand neighbors are parallel. While charge-complementary peptides were previously assumed to organize in an ideal (AB) n pattern, dipolar recoupling measurements on isotopically diluted nanofiber samples reveal a non-negligible amount of self-associated (AA and BB) pairs. Furthermore, computational simulations predict these different structures can coexist within the same nanofiber. Our results highlight structural disorder at the molecular level in a charge-complementary peptide system with implications on co-assembling peptide designs. 

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2. Controlled Lengthwise Assembly of Helical Peptide Nanofibers to Modulate CD8 + T‐Cell Responses

   https://doi.org/10.1002/adma.202003310  

   Fries, Chelsea N. ; Wu, Yaoying ; Kelly, Sean H. ; Wolf, Michelle ; Votaw, Nicole L. ; Zauscher, Stefan ; Collier, Joel H. ( August 2020 , Advanced Materials)

   Peptide nanofibers are useful for many biological applications, including immunotherapy, tissue engineering, and drug delivery. The robust lengthwise assembly of these peptides into nanofibers is typically difficult to control, resulting in polydisperse fiber lengths and an incomplete understanding of how nanofiber length affects biological responses. Here, rationally designed capping peptides control the length of helical peptide nanofibers with unique precision. These designed peptides bind the tips of elongated nanofibers to shorten and narrow their length distributions. Demonstrating their use as immunotherapies, capped nanofibers are preferentially cross‐presented by dendritic cells compared to uncapped nanofibers. Due to increased cross‐presentation, these capped nanofibers trigger stronger CD8⁺T‐cell responses in mice than uncapped nanofibers. This strategy illustrates a means for controlling the length of supramolecular peptide nanofibers to modulate their immunogenicity in the context of immunotherapies.

    

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3. Metal-Promoted Higher-Order Assembly of Disulfide-Stapled Helical Barrels

   https://doi.org/10.3390/nano13192645  

   Agrahari, Ashutosh ; Lipton, Mark ; Chmielewski, Jean ( October 2023 , Nanomaterials)

   Peptide-based helical barrels are a noteworthy building block for hierarchical assembly, with a hydrophobic cavity that can serve as a host for cargo. In this study, disulfide-stapled helical barrels were synthesized containing ligands for metal ions on the hydrophilic face of each amphiphilic peptide helix. The major product of the disulfide-stapling reaction was found to be composed of five amphiphilic peptides, thereby going from a 16-amino-acid peptide to a stapled 80-residue protein in one step. The structure of this pentamer, 5HB1, was optimized in silico, indicating a significant hydrophobic cavity of ~6 Å within a helical barrel. Metal-ion-promoted assembly of the helical barrel building blocks generated higher order assemblies with a three-dimensional (3D) matrix morphology. The matrix was decorated with hydrophobic dyes and His-tagged proteins both before and after assembly, taking advantage of the hydrophobic pocket within the helical barrels and coordination sites within the metal ion-peptide framework. As such, this peptide-based biomaterial has potential for a number of biotechnology applications, including supplying small molecule and protein growth factors during cell and tissue growth within the matrix.

    

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4. A comparison of the collagen triple helix and coiled‐coil peptide building blocks on metal ion‐mediated supramolecular assembly

   https://doi.org/10.1002/pep2.24190  

   Curtis, Ryan W. ; Chmielewski, Jean ( September 2020 , Peptide Science)

   Metal ion‐mediated assembly of peptides is an intriguing method for developing novel biomaterials. In particular, peptide building blocks based on collagen triple helical and coiled‐coil peptides have been functionalized with metal‐binding ligands and assemble into hierarchical structures with diverse potential applications. This review outlines the use of metal‐mediated assembly with these supramolecular structures and highlights how changes in the building blocks lead to significant differences in structural morphologies, with the identity of the metal‐binding ligands and their placement on the building block as crucial aspects in the bottom‐up development of the assemblies.

    

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5. Modular self-assembly of gamma-modified peptide nucleic acids in organic solvent mixtures

   https://doi.org/10.1038/s41467-020-16759-8  

   Kumar, Sriram ; Pearse, Alexander ; Liu, Ying ; Taylor, Rebecca E. ( June 2020 , Nature Communications)

   Nucleic acid-based materials enable sub-nanometer precision in self-assembly for fields including biophysics, diagnostics, therapeutics, photonics, and nanofabrication. However, structural DNA nanotechnology has been limited to substantially hydrated media. Transfer to organic solvents commonly used in polymer and peptide synthesis results in the alteration of DNA helical structure or reduced thermal stabilities. Here we demonstrate that gamma-modified peptide nucleic acids (γPNA) can be used to enable formation of complex, self-assembling nanostructures in select polar aprotic organic solvent mixtures. However, unlike the diameter-monodisperse populations of nanofibers formed using analogous DNA approaches,γPNA structures appear to form bundles of nanofibers. A tight distribution of the nanofiber diameters could, however, be achieved in the presence of the surfactant SDS during self-assembly. We further demonstrate nanostructure morphology can be tuned by means of solvent solution and by strand substitution with DNA and unmodified PNA. This work thereby introduces a science ofγPNA nanotechnology.

    

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