Physical Isolation of Single Protein Molecules within Well‐Defined Coordination Cages to Enhance Their Stability

Encapsulation of a single protein within a confined space can lead to distinct properties compared to bulk solutions, but controlling the number of encapsulated proteins and their environment remains challenging. This study demonstrates the encapsulation of single proteins within well-defined, tunable cavities of self-assembled coordination cages, thereby enhancing protein stability. Within uniform cavities of size-tunable coordination cages, 15 different proteins of varying sizes (3-6 nm in diameter) and properties (e.g., isoelectric points and hydrophobicity) were successfully confined. Various analytical techniques confirmed that the proteins maintained their secondary structures and enzymatic activities under denaturing conditions such as exposure to organic solvents, heat, and buffers. These findings suggest that such coordination cages have the potential to serve as synthetic hosts for precisely controlling protein functions within their customizable cavities.