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Although the in vivo function of the Drosophila melanogaster Hox protein Ultrabithorax (Ubx) is to regulate transcription, in vitro Ubx hierarchically self-assembles to form nanoscale to macroscale materials. The morphology, mechanical properties, and functionality (via protein chimeras) of Ubx materials are all easily engineered. Ubx materials are also compatible with cells in culture. These properties make Ubx attractive as a potential tissue engineering scaffold, but to be used as such they must be biocompatible and nonimmunogenic. In this study, we assess whether Ubx materials are suitable for in vivo applications. When implanted into mice, Ubx fibers attracted few immune cells to the implant area. Sera from mice implanted with Ubx contain little to no antibodies capable of recognizing Ubx. Furthermore, Ubx fibers cultured with macrophages in vitro did not lyse or activate the macrophages, as measured by TNF-α and NO secretion. Finally, Ubx fibers do not cause hemolysis when incubated with human red blood cells. The minimal effects observed are comparable with those induced by biomaterials used successfully in vivo. We conclude Ubx materials are biocompatible and nonimmunogenic.

A key advantage of protein-based materials is the potential to directly incorporate novel functions via gene fusion to produce a single chimeric polypeptide capable of both self-assembly and the desired activity. However, facile production of functionalized protein materials is frequently hampered by the need to trigger materials assembly using conditions that will not irreversibly damage the functional protein. In contrast, the recombinant Drosophila melanogaster transcription factor Ultrabithorax (Ubx) rapidly self-assembles under mild, aqueous conditions to form highly extensible materials with a variety of morphologies. Here, it is demonstrated that materials composed of Ubx chimeras with Enhanced Green Fluorescent Protein (EGFP), mCherry, luciferase, or myoglobin display the functions of the appended proteins, indicating that these activities are neither impaired by the assembly process nor by confinement within the materials. Finally, methods are established that combine EGFP-Ubx and mCherry-Ubx monomers to self-assemble materials patterned on the microscale to macroscale. The self-adhesive properties of Ubx materials also permit manual construction and patterning of more complex forms. The ability to easily functionalize and pattern protein-based materials greatly expands their potential utility in a wide variety of applications.