Enzyme-Instructed Self-Assembly for Cellular Supramolecular Chemistry

Enzyme-instructed self-assembly (EISA) utilizes endogenous enzymatic activity to transform soluble precursors into self-assembling species, allowing for the precise formation of supramolecular nanostructures within cellular environments. This approach offers context-dependent control over assembly, distinguishing it from other methods triggered by pH, redox, or light. EISA serves as a framework for supramolecular chemical biology, mimicking higher-order protein assemblies and linking molecular design with cellular function. It enables programmable conformational and morphological changes, growth factor-mimicking assemblies, and the creation of artificial supramolecular architectures in situ. The perspective suggests expanding EISA beyond alkaline phosphatases to multi-enzyme networks, advancing adaptive biomaterials, programmable therapeutics, and synthetic cellular machines.