Unraveling the Hierarchical Self‐Assembly of Amphiphilic Block Copolymer‐Peptide Conjugates by Tip‐Enhanced Raman Spectroscopy

Abstract Self‐assembly of block copolymers in solution provides access to different nanostructures depending on block composition and processing conditions. However, more complex hierarchical nanostructures as found in nature remain challenging to achieve. In this study, the influence of a β‐sheet forming tetrapeptide sequence (GFFG) is investigated at the interface of an amphiphilic block copolymer based on poly(butyl acrylate) (PBA) and poly(ethylene oxide) (PEO). Using atomic force microscopy (AFM) and tip‐enhanced Raman spectroscopy (TERS), nanoscale insights are provided into the structural organisation and mechanical properties of these hybrid materials. Both the tetrapeptide‐containing block copolymer and a control block copolymer without the peptide linker form wormlike micelles in water. However, the incorporation of the peptide linker alters the micelle morphology by increasing the contour length sixfold compared to the control polymer and by altering the mechanical properties of the wormlike micelles. TERS analysis confirms the presence of ordered β ‐sheet structures at the hydrophilic/hydrophobic interface, which increase the bending stiffness of the micelles. The introduction of additional secondary interactions, such as those induced by the peptide linker, therefore appears as an interesting lever to manipulate the structure formation and mechanical properties block copolymer micelles, opening up interesting design strategies for tailor‐made hierarchically structured nanomaterials.