Amino Acid Sequence in Constitutionally Isomeric Tetrapeptide Amphiphiles Dictates Architecture of One-Dimensional Nanostructures

The switching of two adjacent amino acids can lead to differences in how proteins fold thus affecting their function. This effect has not been extensively explored in synthetic peptides in the context of supramolecular self-assembly. Toward this end, we report here the use of isomeric peptide amphiphiles as molecular building blocks to create one-dimensional (1D) nanostructures. We show that four peptide amphiphile isomers, with identical composition but a different sequence of their four amino acids, can form drastically different types of 1D nanostructures under the same conditions. We found that molecules with a peptide sequence of alternating hydrophobic and hydrophilic amino acids such as VEVE and EVEV self-assemble into flat nanostructures that can be either helical or twisted. On the other hand, nonalternating isomers such as VVEE and EEVV result in the formation of cylindrical nanofibers. Furthermore, we also found that when the glutamic acid is adjacent to the alkyl tail the supramolecular assemblies appear to be internally flexible compared to those with valine as the first amino acid. These results clearly demonstrate the significance of peptide side chain interactions in determining the architectures of supramolecular assemblies

Self-Healing, Self-Assembled β‑Sheet Peptide–Poly(γ-glutamic acid) Hybrid Hydrogels

Self-assembled biomaterials are an important class of materials that can be injected and formed <i>in situ</i>. However, they often are not able to meet the mechanical properties necessary for many biological applications, losing mechanical properties at low strains. We synthesized hybrid hydrogels consisting of a poly­(γ-glutamic acid) polymer network physically cross-linked via grafted self-assembling β-sheet peptides to provide non-covalent cross-linking through β-sheet assembly, reinforced with a polymer backbone to improve strain stability. By altering the β-sheet peptide graft density and concentration, we can tailor the mechanical properties of the hydrogels over an order of magnitude range of 10–200 kPa, which is in the region of many soft tissues. Also, due to the ability of the non-covalent β-sheet cross-links to reassemble, the hydrogels can self-heal after being strained to failure, in most cases recovering all of their original storage moduli. Using a combination of spectroscopic techniques, we were able to probe the secondary structure of the materials and verify the presence of β-sheets within the hybrid hydrogels. Since the polymer backbone requires less than a 15% functionalization of its repeating units with β-sheet peptides to form a hydrogel, it can easily be modified further to incorporate specific biological epitopes. This self-healing polymer−β-sheet peptide hybrid hydrogel with tailorable mechanical properties is a promising platform for future tissue-engineering scaffolds and biomedical applications

Electrospinning Bioactive Supramolecular Polymers from Water

Electrospinning is a high-throughput, low-cost technique for manufacturing long fibers from solution. Conventionally, this technique is used with covalent polymers with large molecular weights. We report here the electrospinning of functional peptide-based supramolecular polymers from water at very low concentrations (<4 wt %). Molecules with low molecular weights (<1 kDa) could be electrospun because they self-assembled into one-dimensional supramolecular polymers upon solvation and the critical parameters of viscosity, solution conductivity, and surface tension were optimized for this technique. The supramolecular structure of the electrospun fibers could ensure that certain residues, like bioepitopes, are displayed on the surface even after processing. This system provides an opportunity to electrospin bioactive supramolecular materials from water for biomedical applications

Self-Assembled 2D Free-Standing Janus Nanosheets with Single-Layer Thickness

We report the thermodynamically controlled growth of solution-processable and free-standing nanosheets via peptide assembly in two dimensions. By taking advantage of self-sorting between peptide β-strands and hydrocarbon chains, we have demonstrated the formation of Janus 2D structures with single-layer thickness, which enable a predetermined surface heterofunctionalization. A controlled 2D-to-1D morphological transition was achieved by subtly adjusting the intermolecular forces. These nanosheets provide an ideal substrate for the engineering of guest components (e.g., proteins and nanoparticles), where enhanced enzyme activity was observed. We anticipate that sequence-specific programmed peptides will offer promise as design elements for 2D assemblies with face-selective functionalization