Spatially Controlled Supramolecular Polymerization of Peptide Nanotubes by Microfluidics

Abstract

Despite the importance of spatially resolved selfassembly for molecular machines,t he spatial control of supramolecular polymerization with synthetic monomers had not been experimentally established. Now,amicrofluidicregulated tandem process of supramolecular polymerization and droplet encapsulation is used to control the position of selfassembled microfibrillar bundles of cyclic peptide nanotubes in water droplets.T his method allows the precise preferential localization of fibers either at the interface or into the core of the droplets.U Vabsorbance,c ircular dichroism and fluorescence microscopyindicated that the microfluidic control of the stimuli (changes in pH or ionic strength) can be employed to adjust the packingd egree and the spatial position of microfibrillar bundles of cyclic peptide nanotubes.Additionally,this spatially organized supramolecular polymerization of peptide nanotubes was applied in the assembly of highly ordered twodimensional droplet networks.Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.

Nanoscale Assembly of Functional Peptides with Divergent Programming Elements

“…The incorporation of d -amino acids into l -peptides can lead to unexpected effects on conformation, self-assembly, and even therapeutic activity, as recently reviewed. 20 Research is revealing the use of heterochirality to fine-tune peptide self-assembly into a variety of nanostructures, including twisted nanofibrils, 21 , 22 nanotapes, 23 , 24 nanotubes, 25 , 26 2D-sheets, 27 or gels. 28 , 29 d -amino acids can inhibit pathological amyloid aggregation, as with d -Phe 30 on l -Phe fibrillization linked to phenylketonuria, 31 or d -Trp-Aib (Aib = aminoisobutyrric acid) on Alzheimer’s disease-related Aβ peptide.…”

Bottom-up supramolecular assembly in two dimensions

“…65 In this design, interlayer Leu-Leu contacts at specific angles afforded staggered nanotubular bilayers, providing an excellent monomer scaffold for further functionalisation in all three dimensions. 77,78 The examples in Figure 2 showcase the ability of directional interactions, such as H-bonding, and nanotube interfaces to guide the hydrophobic packing of monomers, which becomes evident in the perfect alignment of monomers throughout the entire internal structure these 2D assemblies.…”

Synthetic Supramolecular Systems in Life-like Materials and Protocell Models

“…Alternatively, charge repulsions between cyclic peptides can be screened by the addition of small electrolytes to induce nanotube formation and bundling. 38 The confined and localized fibrillation of these cyclic peptides at the center or interface of droplets emulates the spatially controlled supramolecular ). 28 (B) Application of these multimeric coiled-coil barrels as artificial receptors with multiple binding sites within their hydrophobic center.…”

“…Scale bars: 25 mm. Reprinted with permission from Mé ndez-Ardoy et al38 Copyright 2020 Wiley-VCH. (C) Sequential 1D-to-2D self-assembly of amphiphilic cyclic peptides into supramolecular nanosheets stabilized by lateral leucine zippers between adjacent nanotubes.…”