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

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.

Solute–Solvent Interactions in Modern Physical Organic Chemistry: Supramolecular Polymers as a Muse

“…(b) Space filling model of the peptide amphiphile studied by Stevens and co-workers, showing how various alcohol cosolvents solvate the amphiphile surface. 168 Image reproduced from ref ( 168 ). Copyright 2019 the American Chemical Society.…”

1D to 2D Self Assembly of Cyclic Peptides

“…15 Directed DNA and protein folding at the nanoscale have allowed the preparation of 2D biocompatible materials. 3,[16][17][18] In particular, peptide-based scaffolds that undergo 2D selfassembly 19,20 include peptides, [21][22][23][24] proteins, 21,25,26 peptoids 27,28 and derivatives thereof, 29,30 which have found applications in sensing, 27,31 catalysis 24 and molecular biology. 22 However, despite remarkable progress in synthetic supramolecular systems, a synthetic small molecule with different pre-programmed levels of hierarchical self-assembly and adaptive behaviour has remained elusive.…”

Enzyme Instructed Self‐assembly of Naphthalimide‐dipeptide: Spontaneous Transformation from Nanosphere to Nanotubular Structures that Induces Hydrogelation

“…Supramolecular hydrogels of many reported peptide molecules self‐assembled into nanofibrillar morphology with the smallest possible width size, which is much less than 50 nm . Few examples of higher‐order self‐assembled aggregates are also known in the literature . Understanding the self‐assembly mechanism for the formation of such large aggregates is of significant importance but remains challenging.…”

“…[27] Few examples of higher-order self-assembled aggregates are also known in the literature. [19,38,39] Understanding the selfassembly mechanism for the formation of such large aggregates is of significant importance but remains challenging. In this work, we conducted a systematic investigation of the NI-FYp system to elucidate the possible mechanism of nanotubular formation.…”