Mapping In Situ the Assembly and Dynamics in Aqueous Supramolecular Polymers

Supramolecular polymers, molecular assemblies bonded through directional non-covalent interactions, closely mimic the dynamic and adaptive behavior of biological nanofibers, such as those in the cytoskeleton and extracellular matrices. Despite their immense potential, the complexity of assembly pathways makes it highly challenging to unravel the nature of supramolecular dynamics within these assemblies in aqueous environments. Here we introduce a precise combinatorial titration methodology to probe in situ the assembly process of peptide amphiphiles (PAs) as a model system. This approach reveals a binary assembly mechanism, governed by the assembly equilibrium between spheroidal micelles and β-sheet polymers. A reduction in hydrogen bonding strength shifts the equilibrium towards small aggregates and decreases the internal structural order of filamentous supramolecular polymers, promoting the dynamic motion of the constituent monomers. Extending this methodology to two-component copolymerization systems, we find a surprising tendency to form blocky nanostructures with a reduced degree of internal phase separation as the mismatch in peptide sequence decreases. Interestingly, while well-mixed copolymers acquire different dynamics, mismatched ones retain the characteristic supramolecular motion of their homopolymer counterparts. Our approach provides critical insights into supramolecular dynamics, thereby offering new strategies to tailor the dynamic functions in the assemblies of supramolecular nanomaterials.