Protein Bricks: 2D and 3D Bio‐Nanostructures with Shape and Function on Demand

Precise patterning of polymer‐based biomaterials for functional bio‐nanostructures has extensive applications including biosensing, tissue engineering, and regenerative medicine. Remarkable progress is made in both top‐down (based on lithographic methods) and bottom‐up (via self‐assembly) approaches with natural and synthetic biopolymers. However, most methods only yield 2D and pseudo‐3D structures with restricted geometries and functionalities. Here, it is reported that precise nanostructuring on genetically engineered spider silk by accurately directing ion and electron beam interactions with the protein's matrix at the nanoscale to create well‐defined 2D bionanopatterns and further assemble 3D bionanoarchitectures with shape and function on demand, termed “Protein Bricks.” The added control over protein sequence and molecular weight of recombinant spider silk via genetic engineering provides unprecedented lithographic resolution (approaching the molecular limit), sharpness, and biological functions compared to natural proteins. This approach provides a facile method for patterning and immobilizing functional molecules within nanoscopic, hierarchical protein structures, which sheds light on a wide range of biomedical applications such as structure‐enhanced fluorescence and biomimetic microenvironments for controlling cell fate.