Three-Dimensional Visualization of Proteins within Metal-Organic Frameworks

Electron tomography holds great promise as a tool for investigating the three-dimensional (3D) morphologies and internal structures of metal-organic frameworks (MOFs). Understanding the 3D spatial arrangement and density of proteins within protein@MOF biocomposites is paramount for developing synthetic methods to control the location of proteins within the MOF material. The direct visualization of the protein Ferritin (Fn) in Fn@MOF biocomposites was probed through a combination of scanning electron microscopy (SEM), transmission electron microscopy (TEM), and electron tomography (ET). Using con-trolled-dose dry-cryogenic electron tomography (dry-cryoET), we obtain a direct 3D visualization of protein@MOFs with individual protein resolution. These direct observations show that ligand-to-metal ratios for Fn@MOF biocomposites can be tuned to change the spatial arrangement and localization of the proteins within the MOF crystals.