Solvent Effects on the Self-Assembly of an Amphiphilic Polypeptide Incorporating α-Helical Hydrophobic Blocks

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.