The
self-assembly of biological molecules is an important pathway
to understanding the molecular basis of complex metabolic events.
The presence of a cosolvent in an aqueous solution during the self-assembly
process can promote the formation of kinetically trapped metastable
intermediates. In nature, a category of cosolvents termed osmolytes
can work to strengthen the hydrogen-bond network of water such that
the native states of certain proteins are favored, thus modulating
their function and stability. However, identifying cosolvents that
act as osmolytes in biomimetic applications, such as the self-assembly
of soft materials, remains challenging. The present work examined
the effects of ethanol (EtOH) and acetonitrile (ACN) as cosolvents
on the self-assembly of the amphiphilic polypeptide PSar30-(l-Leu-Aib)6 (S30L12), which incorporates α-helical
hydrophobic blocks, in aqueous solution. The results provided a direct
observation of morphological behavior of S30L12 as a function of solvent
composition. Morphological transitions were investigated using transmission
electron microscopy, while the packing of peptide molecules was assessed
using circular dichroism analyses and evaluations of membrane fluidity.
In the EtOH/H2O mixtures, the EtOH strengthened the hydrogen-bond
network of the water, thus limiting the hydrophobic hydration of S30L12
assemblies and enhancing hydrophobic interactions between assemblies.
In contrast, ACN formed self-associated nanoclusters in water and
at the hydrophobic cores of peptide assemblies to stabilize the edges
exposed to bulk water and enhance the assembly kinetics. Fourier transform
infrared (FT-IR) analysis indicated that both EtOH and ACN can modify
the self-assembly of biomaterials in the same manner as osmolyte protectants
or denaturants.