(741g) Engineering and Functionalizing Protein-Based Materials

The development of materials with diverse mechanical and functional properties enables a broad range of applications. For materials composed of protein, well-established molecular biology techniques can theoretically be used to alter the mechanical and functional properties of materials. However, repetition of amino acid sequences in the constituent proteins can complicate engineering the mechanical properties. Furthermore, most protein-based materials are assembled under denaturing conditions, thus precluding incorporation of full-length proteins in an active state. Our lab discovered that the Drosophila melanogaster transcription factor Ultrabithorax (Ubx) self-assembles into materials. These materials are stabilized by specific dityrosine bonds that spontaneously form during assembly. The location of the participating tyrosines in unique sequence motifs enables the reliable tuning of the materials by mutagenesis to be either weaker or stronger. Because Ubx materials rapidly form in mild, aqueous buffers, a surprisingly wide variety of proteins can be incorporated via gene fusion without harming either materials assembly or the function of the appended protein. Indeed, when Ubx is fused to angiogenic growth factors, the resulting fibers control cell signaling and cell behavior in vitro, and can instigate and guide blood vessel formation in vivo. Finally, Ubx proteins in materials retain the ability to bind specific DNA sequences with high affinity. Ubx materials provide an inexpensive and facile platform for customizing materials for a variety of applications.