Dr. Sarah Bondos from Texas A&M University will present “Functionalizing protein-based materials with biomolecules” to the department.
A major challenge in the materials field is the development of bioactive materials that can manipulate or respond to their environment. Theoretically, materials composed of proteins have an enormous advantage, since most of the desired functions can be imparted by proteins. By fusing the gene that encodes the functional protein to the gene that encodes a self-assembling protein, a fusion protein can be easily produced in bacteria that should both mediate the function of interest and self-assemble into useful materials. The gene fusion approach bypasses common problems, such as loss due to diffusion for non-covalent attachment, or protein inactivation and toxic residues for chemical crosslinking approaches. However, the success of this approach has been limited because self-assembling proteins, when artificially produced, often require harsh (denaturing) conditions to trigger materials formation. These conditions unfold and inactivate any appended functional proteins. In contrast, we have accidentally discovered that the Drosophila Hox transcription factor Ultrabithorax (Ubx) will hierarchically self-assemble in vitro into mechanically robust, biocompatible materials spanning the nanoscale to macroscale size regimes. Materials assembly occurs rapidly in mild aqueous buffers, and thus proteins appended by gene fusion retain their activity. Conversely, the appended proteins do not alter Ubx materials assembly.
As a Hox transcription factor, the Ubx protein contains a homeodomain, which binds DNA with remarkably high affinity. This homeodomain remains intact in the materials, and the materials bind DNA in a sequence-specific manner. Thus the DNA can be oriented on the surface of Ubx materials based on the placement of Ubx binding sites. Materials binding also helps protect the DNA from degradation. Thus Ubx provides a remarkably facile system for creating materials functionalized with two key types of biomolecules: protein and DNA.