Modulation of Mechanical Properties of Short Bioinspired Peptide Materials by Single Amino-Acid Mutations

Abstract

The occurrence of modular peptide repeats in load-bearing (structural) proteins is common in nature, with distinctive peptide sequences that often remain conserved across different phylogenetic lineages. These highly conserved peptide sequences endow specific mechanical properties to the material, such as toughness or elasticity. Here, using bioinformatic tools and phylogenetic analysis, we have identified the GX8 peptide with the sequence GLYGGYGX (where X can be any residue) in a wide range of organisms. By simple mutation of the X residue, we demonstrate that GX8 can be self-assembled into various supramolecular structures, exhibiting vastly different physicochemical and viscoelastic properties, from liquid-like coacervate microdroplets to hydrogels to stiff solid materials. A combination of spectroscopic, electron microscopy, mechanical, and molecular dynamics studies is employed to obtain insights into molecular scale interactions driving self-assembly of GX8 peptides, underscoring that π−π stacking and hydrophobic interactions are the drivers of peptide self-assembly, whereas the X residue determines the extent of hydrogen bonding that regulates the macroscopic mechanical response. This study highlights the ability of single amino-acid polymorphism to tune the supramolecular assembly and bulk material properties of GX8 peptides, enabling us to cover a broad range of potential biomedical applications such as hydrogels for tissue engineering or coacervates for drug delivery.

l-Histidine Salt-Bridged Monomer Preassembly and Polymerization-Induced Electrostatic Self-Assembly

“…To understand the segment salt bridges, His100 homopolymer lamellae were studied using FTIR spectroscopy. The H-bonded N–H stretching vibrations of amide/imidazolium (3418, 3275 cm –1 ), amide I/II (1630, 1531 cm –1 ), and imidazolium N–H and COO̅ (1203, 1395 cm –1 ) , are detected comparing to the counterpart dried at pH 1.0 (Figure S15). Dispersion became incrementally milky at pH 4.3 (Figure S16), suggesting an electrostatically tuned phase transition.…”

Bioinspired Squid Peptides─A Tale of Curiosity-Driven Research Leading to Unforeseen Biomedical Applications

“…(j) GW8 peptide coacervates coalescing. Reproduced with permission from ref , copyright 2023, American Chemical Society.…”

Self-assembled aggregates based on cationic amphiphilic peptides: structural insight

“…The self-assembling behavior of peptides is deeply affected by the amino acid composition and by the hydrophobic/hydrophilic balance within the sequence. 20 This latter feature can be modulated by peptide functionalization with polymeric or organic moieties. For instance, derivatization of a peptide with PEG (polyethylene glycol) 21,22 or with glycosyl groups 23 allows increasing its solubility; in contrast, the addition of alkyl chains 24,25 or aromatic moieties [26][27][28] causes a decrease in its solubility.…”