Engineering Protein-Based Biomaterials—Versatile Applications in Biocatalysis, Bioelectronics, Sensing, Imaging and Therapy

Ordered protein-based biomaterials are highly desirable for a wide range of applications including templating, coating, sensing, bioelectronics, catalysis, and biomedicine. This has recently spurred the development, among others, of novel self-assembled materials and supramolecular nanostructures based on biomolecules. Inspired by nature, we explore biomolecules and their derivatives as novel biomedical and technological tools. Among biomolecules, proteins rise huge interest due to their high structural and functional versatility, biocompatibility, and biodegradability. In particular, we mainly focus on a class of engineered repeat proteins, due to their stability and robustness as a base scaffold that can be easily tailored to endow desired functions to the protein and to encode defined supramolecular assembly properties resulting into functional biomaterials.<br/><br/>We have explored strategies that rely on rational design of protein self-assembly and the re-engineering interactions within innate protein-protein contacts in crystalline lattices. On one hand, we demonstrate the potential to generate diverse crystalline protein frameworks by tuning the innate metal coordination preferences, guiding protein assembly for engineered consensus tetratricopeptide repeat (CTPR) proteins.<b>^[1]</b> On the other hand, we have developed strategies to create ordered protein-based biomaterials by re-engineering protein-protein interactions that maintain the crystalline lattices, and by interfacing proteins with other self-assembly elements such as amyloid-derived peptides. Through these methods, we direct the assembly of proteins into structured thin films, 2D monolayers, or 3D tubular architectures.<b>^[2]</b><br/><br/>Additionally, we have developed protein-metal hybrids by engineering metal-binding residues, and the subsequent formation of tailored nanomaterials stabilized by proteins with unique luminescent, magnetic, or catalytic properties. Generally, the fusion of two distinct materials exploits the best properties of each, however, in protein-nanomaterial hybrids, the fusion takes on a new dimension as new properties arise. Overall, the rational engineering of protein-based materials offers a promising approach for biomolecular materials with defined structural and functional properties. We present selected applications of these materials in the fields of bioelectronics,<b>^[3,4]</b> and biomedicine.<b>^[5,6]</b><br/><br/><b>[1] </b>Liutkus, A…., Cortajarena, A,L., <i>Protein Science </i>(2024), 33: e4971.<br/><b>[2] </b>Sanchez-deAlcazar, D…., Cortajarena, A,L, <i>Nanoscale Adv.</i> (2019) 1: 3980-3991.<br/><b>[3] </b>Dominguez Alfaro, A…., Cortajarena, A,L., <i>Small </i>(2022): 2307536<b>.</b><br/><b>[4] </b>Mejias, SH…., Cortajarena, A,L, <i>Nanoscale</i> (2021) 13: 6772-6779.<br/><b>[5] </b>Aires, A. .. Cortajarena, AL, <i>Chem Science</i> <b>12</b> (2021), 2480-2487.<br/><b>[6] </b>Uribe, KB … Cortajarena, AL, <i>Acc. Chem. Re</i>s. <b>54</b> (2021), 4166-4177.