Electrostatic-Driven Lamination and Untwisting of β‑Sheet Assemblies

July 28, 2017

Title

Electrostatic-Driven Lamination and Untwisting of β‑Sheet Assemblies

Author

Yang Hu, Ran Lin, Pengcheng Zhang, Joshua Fern, Andrew G. Cheetham, Kunal Patel, Rebecca Schulman, Chengyou Kan, Honggang Cui

Year

2016

Journal

ACS Nano

Abstract

Peptides or peptide conjugates capable of assembling into one-dimensional (1D) nanostructures have been extensively investigated over the past two decades due to their implications in human diseases and also their interesting applications as biomaterials. While many of these filamentous assemblies contain a β-sheet-forming sequence as the key design element, their eventual morphology could assume a variety of shapes, such as fibrils, ribbons, belts, or cylinders. Deciphering the key factors that govern the stacking fashion of individual β-sheets will help understand the polymorphism of peptide assemblies and greatly benefit the development of functional materials from customized molecular design. Herein, we report the decisive role of electrostatic interactions in the lamination and untwisting of 1D assemblies of short peptides. We designed and synthesized three short peptides containing only six amino acids (EFFFFE,KFFFFK, and EFFFFK) to elucidate the effective control of β-sheet stacking. Our results clearly suggest that electrostatic repulsions between terminal charges reduce the pitch of the twisting β-sheet tapes, thus leading to highly twisted, intertwined fibrils or twisted ribbons, whereas reducing this repulsion, either through molecular design of peptide with opposite terminal charges or through coassembly of two peptides carrying opposite charges, results in formation of infinite assemblies such as belt-like morphologies. We believe these observations provide important insight into the generic design of β-sheet assemblies.

Instrument

J-710

Keywords

Circular dichroism, Protein folding, Nanostructures, Materials, Biochemistry