Designing Peptide‐Based Supramolecular Biomaterials

Abstract

One rapidly emerging area where supramolecular chemistry can have a significant impact is in biomaterials science, and specifically in the design of cell‐contacting biomaterials. Aspects that are known to influence cell behavior at any particular time include chemical signals, mechanical properties (i.e., gel stiffness), and topographical signals related to fiber sizes and alignment. In this chapter, we provide an overview of current supramolecular chemistry strategies in the design of cell scaffolds based on peptides and their derivatives. The approaches discussed include those inspired by secondary or quaternary structures (α‐helix, β‐sheet, collagen triple helix) found in natural proteins as well as synthetic sequences such as aromatic and aliphatic peptide amphiphiles. We then discuss how supramolecular fibers based on peptides can be designed to control and direct (stem) cell behavior by engineering stiffness and chemical presentation of bioactive ligands.

Multicomponent peptide assemblies

“…β -Sheet peptides are among the most widely used self-assembling peptide motifs in synthetic biomaterials. 23,26,27,180,181 Zhang et al . pioneered the design of self-assembling amphipathic, ionic complementary peptides with alternating hydrophobic and hydrophilic residues upon discovering the facile self-assembly and hydrogel formation of the EAK16 peptide, which was initially identified in the yeast Zuotin protein (Figure 4).…”

“…476,477 Central tri-substituted aromatic molecules decorated with three peptides undergo assembly-induced aggregation to form triple β-sheet nanofibrils in aqueous solutions. 23 Attaching amphipathic β-sheet pentapeptides with either positive or negative charges to alternating positions around an aromatic core provides symmetrical discotic monomers (Figure 27A) that will only undergo salt-induced self-assembly at neutral pH due to the repulsive effects of the uniform cationic or anionic charge on either system. However, when these discotic peptides are mixed in equimolar ratios, the complementary charge in each system enables the directed coassembly of these materials into nanorod aggregates at neutral pH where both lysine and glutamic acid residues are charged.…”

“…17–20 The abnormal self-assembly of peptides and proteins into amyloid aggregates is characteristic of protein folding disorders, 16,21,22 although the regulated self-assembly of amyloid also gives rise to functional biomaterials. 23–29 These naturally occurring systems have inspired the exploitation of self-assembled peptides and proteins as functional materials, including one- and two-dimensional fibrils and sheets as well as spherical micelles. 30–33 These assembled nano- and microstructures often exhibit emergent properties, such as hydrogelation, that enable these materials to be used for biological applications that include drug delivery, 34–41 regenerative medicine, 42–46 tissue engineering, 47–53 and self-adjuvanting vaccines.…”

Self-assembly of PEGylated tetra-phenylalanine derivatives: structural insights from solution and solid state studies

“…The interaction mode can strongly influence both morphology and properties of the final peptide-based materials. Special interest was recently devoted to peptide self-assembling materials in which aggregation is promoted by aromatic amino acids, such as phenylalanine, tyrosine or tryptophan, where π-stacking interactions occur456. To this regard, a paradigmatic example is represented by the diphenylalanine (FF or F2) peptide, which constitutes the core recognition motif of Alzheimer’s β-amyloid peptide.…”

Amyloid scaffolds as alternative chlorosomes

“…4, 5 This repeating architecture underlies a remarkably efficient light-harvesting capability, powering green sulfur bacteria in the low-light conditions found one hundred meters below sea level. 6, 7 We hope to expand our increasing understanding of assembly pathways for constructing ordered cross-β amyloids ranging from nanotube, 8–13 ribbon, 14–16 sheet, 17–19 and fiber 14, 20–24 architectures for building chlorosome-like arrays. Templating chromophore arrays on protein scaffolds able to sustainably self-propagate in living cells could significantly extend the functions of extant biology.…”