Responsive hybrid hydrogels with volume transitions modulated by a titin immunoglobulin module

The I28 immunoglobulin (Ig)-like module of human cardiac titin, an elastic muscle protein, was used to cross-link acrylamide (AAm) copolymers into hyb rid hydrogels. Cross-linking was accomplished through metal coordination bo nding between terminal histidine tags (His tags) of the I28 module and meta l-chelating nitrilotriacetic acid (NTA)-containing side chains on the copol ymer. In solution, the beta-sheet structure of the I28 module unfolded with a transition midpoint of about 58 degrees C as the temperature was elevate d. Hydrogels cross-linked with the I28 module demonstrated positive tempera ture responsiveness; they swelled to 3 times their initial volume at temper atures above the melting temperature of the cross-links. Positive temperatu re responsiveness is unusual for synthetic hydrogels. The I28 hybrid hydrog els demonstrate that cross-linking synthetic polymers with natural, well-ch aracterized protein modules is a practical strategy for creating new materi als with unique environmental responsiveness predictably determined by the mechanical properties of the protein cross-links. These new materials may b e useful for controlled chemical delivery.