nn8b08117_si_001.pdf (2.56 MB)
Residue-Specific Solvation-Directed Thermodynamic and Kinetic Control over Peptide Self-Assembly with 1D/2D Structure Selection
journal contribution
posted on 2019-01-23, 21:03 authored by Yiyang Lin, Matthew Penna, Michael R. Thomas, Jonathan P. Wojciechowski, Vincent Leonardo, Ye Wang, E. Thomas Pashuck, Irene Yarovsky, Molly M. StevensUnderstanding 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.