Residue-Specific Solvation-Directed Thermodynamic and Kinetic Control over Peptide Self-Assembly with 1D/2D Structure Selection.

Yiyang Lin,Molly M Stevens,E Thomas Pashuck,Jonathan P Wojciechowski,Matthew Penna,Vincent Leonardo,Ye Wang,Irene Yarovsky,Michael R Thomas

doi:10.1021/acsnano.8b08117

Abstract

Understanding the self-organization and structural transformations of molecular ensembles is important to explore the complexity of biological systems. Here, we illustrate the crucial role of cosolvents and solvation effects in thermodynamic and kinetic control over peptide association into ultrathin Janus nanosheets, elongated nanobelts, and amyloid-like fibrils. We gained further insight into the solvation-directed self-assembly (SDSA) by investigating residue-specific peptide solvation using molecular dynamics modeling. We proposed the preferential solvation of the aromatic and alkyl domains on the peptide backbone and protofibril surface, which results in volume exclusion effects and restricts the peptide association between hydrophobic walls. We explored the SDSA phenomenon in a library of cosolvents (protic and aprotic), where less polar cosolvents were found to exert a stronger influence on the energetic balance at play during peptide propagation. By tailoring cosolvent polarity, we were able to achieve precise control of the peptide nanostructures with 1D/2D shape selection. We also illustrated the complexity of the SDSA system with pathway-dependent peptide aggregation, where two self-assembly states (i.e., thermodynamic equilibrium state and kinetically trapped state) from different sample preparation methods were obtained.

Highlights

The study of biologically relevant self-assembly is essential for dissecting the molecular basis of biological events such as protein misfolding and amyloid fibrillation and for guiding the design of biomimetic materials.[1]
We believe that the study of solvation effects in this work can provide a better understanding of biomolecule−solvent interactions and a strategy to thermodynamically and kinetically control the self-assembly of biological molecules of varied structure and function
A thermodynamic energy balance defined by contributions from H-bonding, π−π stacking, and the hydrophobic effect resulted in the formation of Janus nanosheets

Summary

Introduction

The study of biologically relevant self-assembly is essential for dissecting the molecular basis of biological events such as protein misfolding and amyloid fibrillation and for guiding the design of biomimetic materials.[1]. We further investigated the effect of other alcohols on SDSA with ethylene glycol, ethanol, n-propanol, and n-butanol, which have the relative polarity (ETN) of 0.79, 0.654, 0.617, and 0.586, respectively.[51] Unlike methanol, the presence of 5% ethanol in the peptide growth solution led to the formation of elongated nanobelts (Figure 3a), whereas nanofibrils formed with high concentrations of ethanol (10−15%, Figure S2).

Results

Conclusion