Minimalistic peptide supramolecular co-assembly: expanding the conformational space for nanotechnology

Abstract

Molecular self-assembly is a ubiquitous process in nature and central to bottom-up nanotechnology. In particular, the organization of peptide building blocks into ordered supramolecular structures has gained much interest due to the unique properties of the products, including biocompatibility, chemical and structural diversity, robustness and ease of large-scale synthesis. In addition, peptides, as short as dipeptides, contain all the molecular information needed to spontaneously form well-ordered structures at both the nano- and the micro-scale. Therefore, peptide supramolecular assembly has been effectively utilized to produce novel materials with tailored properties for various applications in the fields of material science, engineering, medicine, and biology. To further expand the conformational space of peptide assemblies in terms of structural and functional complexity, multicomponent (two or more) peptide supramolecular co-assembly has recently evolved as a promising extended approach, similar to the structural diversity of natural sequence-defined biopolymers (proteins) as well as of synthetic covalent co-polymers. The use of this methodology was recently demonstrated in various applications, such as nanostructure physical dimension control, the creation of non-canonical complex topologies, mechanical strength modulation, the design of light harvesting soft materials, fabrication of electrically conducting devices, induced fluorescence, enzymatic catalysis and tissue engineering. In light of these significant advancements in the field of peptide supramolecular co-assembly in the last few years, in this tutorial review, we provide an updated overview and future prospects of this emerging subject.

Supramolecular Peptide/Polymer Hybrid Hydrogels for Biomedical Applications

“…The application of supramolecular chemistry principles is becoming increasingly prevalent in biomaterials design to yield properties typical of biological materials (tissues) such as dynamic responsive behavior. This can be achieved through the use of reversible noncovalent interactions among molecular building blocks, notably hydrophobic forces, electrostatic interactions, hydrogen‐bonding, π–π stacking, and van der Waals forces . Noncovalent interactions are relatively weak (2–250 kJ⋅mol −1 ), compared to covalent bonds (100–400 kJ⋅mol −1 ), but when combined synergistically they allow the assembly of stable and well‐defined structures .…”

“…Peptides are commonly used to produce self‐assembling hydrogels. Through their sequence‐defined chemical structure obtained through stepwise synthesis, peptides can provide the desired biological functionality and biodegradability (e.g., incorporation of bioactive sequences from natural proteins) . However, the mechanical properties of self‐assembling peptides are often weak (<kPa) as synthetic peptides are limited by low molecular weight species (short peptides with less than 30 amino acids).…”

The Ultrafast Assembly of a Dipeptide Supramolecular Organogel and its Phase Transition from Gel to Crystal

“…[5] As the pioneering group,G azit and his co-workers have extended the applications of FF-based assemblies from semiconducting into biomedicine and nanofabrication. [5] As the pioneering group,G azit and his co-workers have extended the applications of FF-based assemblies from semiconducting into biomedicine and nanofabrication.…”

Fibrous Aggregates of Short Peptides Containing Two Distinct Aromatic Amino Acid Residues

“…However, none offer the same advantages as peptide‐based materials. In their attempts to design a simple yet robust scaffold, exhibiting the essential properties of natural ECM, Ulijn and co‐workers developed a nanofibrous hydrogel based on co‐assembling peptides, Fmoc‐FF, Fmoc‐RGD, and Fmoc‐RGE . The self‐assembly of Fmoc derivatives of short peptides is believed to be governed by a combination of aromatic stacking interactions and H‐bond formation .…”

“…In their attempts to design a simple yet robust scaffold, exhibiting the essential properties of natural ECM, Ulijn and co-workers developed a nanofibrous hydrogel based on coassembling peptides, Fmoc-FF, Fmoc-RGD, and Fmoc-RGE. [15,16] The self-assembly of Fmoc derivatives of short peptides is believed to be governed by a combination of aromatic stacking interactions and Hbond formation. [17] Another example of a peptidebased scaffold is the mixture of peptides RADA16-I (Ac RADARADARADARADA-NH 2 ) and RADA16-II (Ac-RARA-DADARARADADA-NH 2 ), sold commercially under the trade name PuraMatrixTM.…”