Designing stable, hierarchical peptide fibers from block co-polypeptide sequences.

Mark M J Van Rijt,Mohammad-Amin Moradi,Aimee L Boyle,Alessandro Ianiro,Adriano Ciaffoni,Nico A J M Sommerdijk,Heiner Friedrich,Alexander Kros,Joseph P Patterson

doi:10.1039/c9sc00800d

Abstract

Natural materials, such as collagen, can assemble with multiple levels of organization in solution. Achieving a similar degree of control over morphology, stability and hierarchical organization with equilibrium synthetic materials remains elusive. For the assembly of peptidic materials the process is controlled by a complex interplay between hydrophobic interactions, electrostatics and secondary structure formation. Consequently, fine tuning the thermodynamics and kinetics of assembly remains extremely challenging. Here, we synthesized a set of block co polypeptides with varying hydrophobicity and ability to form secondary structure. From this set we select a sequence with balanced interactions that results in the formation of high-aspect ratio thermodynamically favored nanotubes, stable between pH 2 and 12 and up to 80 °C. This stability permits their hierarchical assembly into bundled nanotube fibers by directing the pH and inducing complementary zwitterionic charge behavior. This block co-polypeptide design strategy, using defined sequences, provides a straightforward approach to creating complex hierarchical peptide-based assemblies with tunable interactions.

Highlights

IntroductionAmphiphilic peptide materials have been shown to organize into various morphologies, such as; spherical-,14–17 and cylindrical micelles,[6,8,18] vesicles,[12,17,19,20,21] nanotubes,[22,23,24,25,26,27,28,29,30] nanoribbons,[25,30,31,32,33,34] and hydrogel networks.[13,35] Nanotubes are de ned as well-de ned hollow cylinders with a diameter range of 0.5–500 nm and an aspect exceeding ve.[36] These morphologies possess only limited levels of organization, which strongly contrast with natural materials like collagen that possess multiple levels of organization (hierarchical materials)
Due to their biocompatibility, biodegradability and their versatility in chemistry,[1,2,3] poly(amino acid) amphiphiles are widely investigated for applications including therapeutics,[4] drug delivery,[5] and scaffolding for biological growth.[6]
Molecular design strategy Using solid-phase peptide synthesis (SPPS),[49] we created a set of block co-polypeptides (BCPP) with the generic composition [ALV]x[KGE]y, see Scheme 1 and Electronic supplementary information (ESI) Section 3.† The hydrophobic alanine – leucine – valine (ALV) sequence is designed to form a rigid secondary structure, either a-helical or b-sheet,[50,51] which makes the formation of typical spherical or cylindrical micelles less favorable as Scheme 1 Molecular structure of [ALV]x[KGE]y and an overview of the investigated peptide sequences

Summary

Introduction

Amphiphilic peptide materials have been shown to organize into various morphologies, such as; spherical-,14–17 and cylindrical micelles,[6,8,18] vesicles,[12,17,19,20,21] nanotubes,[22,23,24,25,26,27,28,29,30] nanoribbons,[25,30,31,32,33,34] and hydrogel networks.[13,35] Nanotubes are de ned as well-de ned hollow cylinders with a diameter range of 0.5–500 nm and an aspect exceeding ve.[36] These morphologies possess only limited levels of organization, which strongly contrast with natural materials like collagen that possess multiple levels of organization (hierarchical materials) As these hierarchical materials possess unrivalled control over structure and properties,[37] achieving hierarchical self-assembly in synthetic materials through additional complementary supramolecular interactions is an important goal in the eld of bioinspired materials. The stability of the nanotube morphology under this broad variety of environments allows their organization in solution to be tuned by controlling inter-nanotube attraction and repulsion, resulting in the formation of bundled nanotube bers

Results and discussion

Conclusions

Funding sources