Self-Repair of Structure and Bioactivity in a Supramolecular Nanostructure

Abstract

Supramolecular nanostructures formed through self-assembly can have energy landscapes, which determine their structures and functions depending on the pathways selected for their synthesis and processing, and on the conditions they are exposed to after their initial formation. We report here on the structural damage that occurs in supramolecular peptide amphiphile nanostructures, during freezing in aqueous media, and the self-repair pathways that restore their functions. We found that freezing converts long supramolecular nanofibers into shorter ones, compromising their ability to support cell adhesion, but a single heating and cooling cycle reverses the damage and rescues their bioactivity. Thermal energy in this cycle enables noncovalent interactions to reconfigure the nanostructures into the thermodynamically preferred long nanofibers, a repair process that is impeded by kinetic traps. In addition, we found that nanofibers disrupted during freeze drying also exhibit the ability to undergo thermal self-repair and recovery of their bioactivity, despite the extra disruption caused by the dehydration step. Following both freezing and freeze drying, which shorten the 1D nanostructures, their self-repair capacity through thermally driven elongation is inhibited by kinetically trapped states, which contain highly stable noncovalent interactions that are difficult to rearrange. These states decrease the extent of thermal nanostructure repair, an observation we hypothesize applies to supramolecular systems in general and is mechanistically linked to suppressed molecular exchange dynamics.

Sequence isomerism-dependent self-assembly of glycopeptide mimetics with switchable antibiofilm properties

“…Oligopeptides' capability of assembling into stimuli-responsive biomimetic superstructures has attracted great attention due to their interesting applications as biomaterials 1–5. The self-assembled superstructures are able to reversibly respond to external stimuli or environmental changes,6–10 which can be used to mimic soft structures in nature such as protein assemblies 11.…”

A self-assembling amphiphilic peptide nanoparticle for the efficient entrapment of DNA cargoes up to 100 nucleotides in length

“…[36][37][38][39][40] Amphipathic peptides are emerging as suitable candidates for fabricating well-ordered nanostructures. [41][42][43][44][45][46][47] To take advantage of the vector properties offered by peptides and at the same time start closing the gap in cargo size between ASOs and entire genes, we intended to establish a purely peptidic, self-assembling delivery system that lends itself to the incorporation of single-and double-stranded DNA segments that are larger than the average ASO. Here, we report a novel amphiphilic peptide henceforth called (HR)3gT that is designed to self-assemble into multi-compartment micellar nanoparticles (MCM-NPs).…”

Current Progress in Cross-Linked Peptide Self-Assemblies

“…Among them, peptide-based fibrous supramolecular assemblies are one of the most attractive platforms to design biomaterials with various bioactivities and structures, and they have recently attracted particular attention. In pioneer works, amphiphilic peptides having hydrophobic alkyl chain at the termini of hydrophilic peptides have been designed, and their fundamental properties and applications to biomaterials have been investigated [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ]. Currently, both amphiphilic peptides and other peptide-based self-assembly units have been found, enabling the design of peptide fibers with a variety of functions [ 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 ,…”