Domain Coordination Governs Pore Architecture in Transient Double-Network Antibody-Binding Polyprotein Hydrogels

Area of Science:

• Biomaterials Science
• Protein Engineering
• Nanotechnology

Background:

• Protein-based hydrogels are promising biomaterials but suffer from poor permeability to large molecules due to dense nanoscale networks.
• Developing protein hydrogels with enhanced permeability is crucial for applications requiring efficient transport of biomolecules.

Purpose of the Study:

• To develop a general strategy for creating highly permeable polyprotein hydrogels.
• To establish a molecular design rule for tuning porosity in folded-protein biomaterials.
• To create advanced protein-based scaffolds with programmable permeability and function.

Main Methods:

• Photochemical cross-linking of engineered octameric repeats of antibody-binding Protein A or Protein L.
• Utilizing a transient alginate network during gelation to control pore formation.
• Investigating the effect of protein coordination capacity on hydrogel network architecture and pore characteristics.

Main Results:

• Achieved highly permeable polyprotein hydrogels by controlling protein coordination during competitive gelation.
• Demonstrated that lower coordination (Protein A) yields larger pores, while higher coordination (Protein L) results in smaller, more numerous pores.
• Engineered hydrogels allow rapid and deep penetration of antibodies throughout the material, maintaining high functional-domain density.

Conclusions:

• Established a molecular design rule for tuning porosity in protein biomaterials based on protein coordination.
• Developed a method for creating highly permeable, protein-based affinity matrices with exceptional binding capacity and stability.
• Opened a route to next-generation, fully protein-based scaffolds with programmable permeability and function for advanced biomaterial applications.