Aromatic stacking facilitated self-assembly of ultrashort ionic complementary peptide sequence: β-sheet nanofibers with remarkable gelation and interfacial properties

Wychowaniec, Jacek K., Patel, Ronak, Leach, James, Mathomes, Rachel, Chhabria, Vikesh, Patil-Sen, Yogita, Hidalgo-Bastida, Araida, Forbes, Robert T., Hayes, Joseph M. and Elsawy, Mohamed A. 2020. Aromatic stacking facilitated self-assembly of ultrashort ionic complementary peptide sequence: β-sheet nanofibers with remarkable gelation and interfacial properties. Biomacromolecules 21 (7) , pp. 2670-2680. 10.1021/acs.biomac.0c00366

Preview

PDF - Published Version Available under License Creative Commons Attribution. Download (7MB) | Preview

Abstract

Understanding peptide self-assembly mechanisms and stability of the formed assemblies is crucial for the development of functional nanomaterials. Herein, we have adopted a rational design approach to demonstrate how a minimal structural modification to a nonassembling ultrashort ionic self-complementary tetrapeptide FEFK (Phe4) remarkably enhanced the stability of self-assembly into β-sheet nanofibers and induced hydrogelation. This was achieved by replacing flexible phenylalanine residue (F) by the rigid phenylglycine (Phg), resulting in a constrained analogue PhgEPhgK (Phg4), which positioned aromatic rings in an orientation favorable for aromatic stacking. Phg4 self-assembly into stable β-sheet ladders was facilitated by π-staking of aromatic side chains alongside hydrogen bonding between backbone amides along the nanofiber axis. The contribution of these noncovalent interactions in stabilizing self-assembly was predicted by in silico modeling using molecular dynamics simulations and semiempirical quantum mechanics calculations. In aqueous medium, Phg4 β-sheet nanofibers entangled at a critical gelation concentration ≥20 mg/mL forming a network of nanofibrous hydrogels. Phg4 also demonstrated a unique surface activity in the presence of immiscible oils and was superior to commercial emulsifiers in stabilizing oil-in-water (O/W) emulsions. This was attributed to interfacial adsorption of amphiphilic nanofibrils forming nanofibrilized microspheres. To our knowledge, Phg4 is the shortest ionic self-complementary peptide rationally designed to self-assemble into stable β-sheet nanofibers capable of gelation and emulsification. Our results suggest that ultrashort ionic-complementary constrained peptides or UICPs have significant potential for the development of cost-effective, sustainable, and multifunctional soft bionanomaterials.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences
Additional Information:	This is an open access article published under a Creative Commons Attribution (CC-BY) License
Publisher:	American Chemical Society
ISSN:	1525-7797
Date of First Compliant Deposit:	27 January 2021
Date of Acceptance:	12 May 2020
Last Modified:	03 May 2023 19:47
URI:	https://orca.cardiff.ac.uk/id/eprint/137967

Citation Data

Cited 22 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item