The interplay between molecular organization and photochemical reactivity underlies function in both biological and synthetic systems. However, resolving the hierarchical architectures that govern these processes in dynamic, hydrated environments remains a major challenge. Here, we demonstrate a bidirectional coupling between peptide amphiphile self-assembly and light-driven alkene reactivity that allows molecular architectures to be both interrogated and reprogrammed using light.
Self-assembly controls which photochemical pathway is accessed. When peptide amphiphiles assemble into ordered nanofibers, attached stilbene groups are brought into defined proximity and orientation, enabling efficient light-induced covalent crosslinking. In contrast, when the assemblies are disrupted, the same molecules undergo a different photochemical response under identical irradiation conditions. Importantly, the light-induced crosslinking converts transient molecular organization into permanent covalent connections, allowing assembly states to be directly read out through photochemical behaviour. At the same time, these photochemical transformations reshape the assemblies themselves. Together, this work establishes photochemistry as a versatile tool to both probe and control hierarchical peptide-based architectures under biologically relevant conditions.