Hydrogel and Organogel Formation by Hierarchical Self‐Assembly of Cyclic Peptides Nanotubes

Abstract

Breaking away from the linear structure of previously reported peptide‐based gelators, this study reports the first example of gel formation based on the use of cyclic peptides made of alternating d‐ and l‐amino acids, known to self‐assemble in solution to form long nanotubes. Herein, a library of cyclic peptides was systemically studied for their gelation properties in various solvents, uncovering key parameters driving both organogel and hydrogel formation. The hierarchical nature of the self‐assembly process in water was characterised by a combination of electron microscopy imaging and small‐angle X‐ray scattering, revealing a porous network of entangled nanofibres composed by the aggregation of several cyclic peptide nanotubes. Rheology measurements then confirmed the formation of soft hydrogels.

Dual self-assembly of supramolecular peptide nanotubes to provide stabilisation in water

“…Nucleases, tubular proteins such as the tobacco mosaic virus and the collagen of our connective tissues all use this hierarchical assembly to form their impressive complex and defined nanostructures. Although synthetically reproducing the complexity of these systems is still a far prospect, the advent of supramolecular polymers has brought us a step closer by providing us with a powerful tool to synthesise a range of different morphologies on the nanoscale, such as nanofibers 1 , nanoribbons 2 and nanotubes 3,4 . These nanostructures consist of repeating subunits (unimers) that can self-assemble over long ranges via directional non-covalent interactions, most commonly π–π stacking 5 , hydrogen bonding 6 and hydrophobic interactions 7 .…”

“…These nanostructures consist of repeating subunits (unimers) that can self-assemble over long ranges via directional non-covalent interactions, most commonly π–π stacking 5 , hydrogen bonding 6 and hydrophobic interactions 7 . Many of these systems have been optimised to form very large elongated assemblies, typically nanofibers, which create supramolecular gel networks 3,8–11 . Recent advancements in supramolecular systems have led to them being used in a wide range of applications, in optoelectronics 12,13 , self-healable materials 14 or bio-therapeutics 15–17 .…”

Spatially Controlled Supramolecular Polymerization of Peptide Nanotubes by Microfluidics

“…Supramolecular microfibers made of bundles of hollow nanotubes can be obtained by one‐dimensional (1D) hierarchical assembly of the suitable cyclic peptide monomers (CP) . These dynamic structures can be employed to mimic the physical properties of more complex natural fibrillar networks and function as storage or transport systems –.…”

Light‐Fuelled Self‐Assembly of Cyclic Peptides into Supramolecular Tubules

“…[13] The primary supramolecular interactions that allow self-assembly of cyclic peptides into tubules are the betasheet-type hydrogen bonding motives. In our design, we chose leucine as the only D-amino acid because leucine-rich cyclic peptides are known to form long and stiff supramolecular polymers, [14,15] through attractive hydrophobic interactions. Hydrogen-bonding and hydrophobic interactions are attractive interactions that can be counterbalanced by electrostatic repulsion to prevent the formation of aggregates.…”

“…Typically, we have harnessed the charges carried by glutamic acid (pK a = 4.15) [13] and histidine (pK a = 6.04), [16,17] to design pHresponsive cyclic peptides. [15,18] Specifically, the cyclic peptide (CP) on which we focus here contains three glutamic acid residues (Scheme 1). Further, a pyrene moiety was introduced because its aggregation-dependent fluorescence allows probing CP self-assembly.…”