pH‐Responsive Capsules with a Fibril Scaffold Shell Assembled from an Amyloidogenic Peptide

Abstract

of highly ordered, linear amyloids fibrils. Amyloids have originally been associated with neurodegenerative disorders. [1][2][3] More recently, however, amyloid-forming peptide and protein building blocks have been increasingly discovered in functional roles in a range of organisms. [4,5] This finding has given inspiration for efforts focused on exploring the application of amyloids for artificial functional bio-inspired materials. [4,[6][7][8] In this context, short peptides with predictable and defined assembly behavior have emerged as potential building blocks for the generation of a versatile set of functional materials. [9][10][11] Moreover, the chemical space offered by the possible amino acid sequences can be further expanded using genetic engineering and chemical functionalisation to allow peptide self-assembly and structural properties to be tailored to present specific properties and functionalities. [12][13][14][15][16] Amyloid and amyloid-like fibrils formed by a range of very different proteins and peptides present considerable similarity in their overall structural and morphological properties even when their sequence shows no common features. [17,18] This observation has given rise to the idea that the amyloid state can be a generally accessible for polypeptide chains and as such, molecular assemblies could be designed by optimizing the chemical composition of the peptide building blocks and their Peptides and proteins have evolved to self-assemble into supramolecular entities through a set of non-covalent interactions. Such structures and materials provide the functional basis of life. Crucially, biomolecular assembly processes can be highly sensitive to and modulated by environmental conditions, including temperature, light, ionic strength and pH, providing the inspiration for the development of new classes of responsive functional materials based on peptide building blocks. Here, it is shown that the stimuli-responsive assembly of amyloidogenic peptide can be used as the basis of environmentally responsive microcapsules which exhibit release characteristics triggered by a change in pH. The microcapsules are biocompatible and biodegradable and may act as vehicles for controlled release of a wide range of biomolecules. Cryo-SEM images reveal the formation of a fibrillar network of the capsule interior with discrete compartments in which cargo molecules can be stored. In addition, the reversible formation of these microcapsules by modulating the solution pH is investigated and their potential application for the controlled release of encapsulated cargo molecules, including antibodies, is shown. These results suggest that the approach described here represents a promising venue for generating pH-responsive functional peptide-based materials for a wide range of potential applications for molecular encapsulation, storage, and release.

Design of Stimuli‐Responsive Peptides and Proteins

“…Heating from 4 to 35 °C Core-shell [13] M-B-ELP M:C14; B 1 : GAGASRGGSGGS; Interfacial tension is reduced as pH increasing [18] DAMP4 MD(PSMKQLADS-LHQLARQ-VSRLEHA) 4 pH 7.5/8.5 Reversible shifting between forming stable foam and collapsing [19] P11-2 CH 3 CO-QQRFQWQFEQQ-NH 2 pH 5 Form stable nematic gels (pH < 5), destabilizing at higher pH [20] EAK-12d AEAEAEAEAKAK pH 3-5 α-helix to β-sheet [21] SgI GSFSIQYTYHV pH 6-10 Gel formation [22] KD AcNH-KGSFSIQYTYHVD-CONH2 pH 7 Random coil to β-sheet rich nanofibril [23] A1H1 AATAVSHTTHHA Shift from neutral to acidic pH Stability of A1H1 β-sheet is reduced and disassembling to random monomers at lower temperatures [24] KPK Poly( L -K)-b-poly (propylene oxide)-b-poly ( L -K) pH 3-7 Random coil to spherical micelle in acidic condition, helix to vesicle or disk micelle in basic condition [25] PLGA-PEG-H 7 K(R 2 ) 2 PLGA-PEG-RRK(HHHHHHH)RR pH 7.4 Self-assemble into polymeric micelles containing PTX (PEX-PM) at neutral pH, expose K(R 2 ) 2 to the surface when pH reduces below 7.4 (acidic) [26] PA1 C 16 H 6 -OEG pH 6-6.5/7.5 Self-assemble into nanofibers at pH 7.5 and disassemble at pH 6-6.5 [27] PA2…”

“…Reproduced with permission. [ 23 ] Copyright 2021, Wiley‐VCH. d) Illustration of thermal hysteresis of A1H1 protein and its disassembling process facilitated by pH reduction.…”

Bioinspired enzymatic compartments constructed by spatiotemporally confined in situ self-assembly of catalytic peptide

“…Beyond the spherical structure of proteins, self-assembly peptides could form variable morphologies, including 1D nanofibers 28 – 31 , nanotubes 32 – 34 , 2D nanosheets 35 , 36 , and even crystal structure 37 – 39 , and these micro-scale structures would be retained in the cavity of GPs to overcome the limitation of the permeability of GPs (i.e., the biomolecular leakage after the encapsulation). Meanwhile, pH 40 – 43 , salt 44 , 45 , and temperature 46 – 48 responsive behaviors of peptide self-assemblies enable them to achieve spatiotemporally controllable assembly in a confined environment. Moreover, recently self-assembly peptides with enzymatic properties have been well studied 49 – 53 , which makes them promising candidates to construct artificial enzymatic compartments instead of natural enzymes.…”

Recent Advances in Peptides-Based Stimuli-Responsive Materials for Biomedical and Therapeutic Applications: A Review

“…(B) pH-induced formation of nano fibrillar peptide capsules from aqueous solution of KD peptide, (C) Three approaches used for the synthesis of peptide microcapsules. Adapted with permission from ref . Copyright 2021 Wiley-VCH.…”

“…Shimanovich et al synthesized pH-responsive KGSFSIQY-TYHVD peptide-based microcapsules, termed KD, for the controlled release of encapsulated cargos including antibodies (see Appendix A). 29 Figure 2 illustrates the pH-induced selfassembly of the KD peptide and the mechanisms involved in the formation of KD microcapsules. The KD peptide was in its monomeric state at low pH (6.5).…”