4.14 Rational and Combinatorial Methods to Create Designer Protein Interfaces ☆

Biomaterials aim to mimic the biophysical and mechanical interactions that cells experience in their natural environment. Natural proteins, however, are often not optimal for use in biomaterials, lacking stability or biological specificity and potency. We provide an overview of main approaches applied for optimizing proteins. Rational engineering leverages knowledge of structure and function for site-directed mutagenesis, protein fusion design, or post-translational modification. Combinatorial engineering involves expression of diverse libraries of protein variants coupled with high-throughput screening for desired phenotypes. Techniques for both approaches will be described, followed by discussion of considerations and challenges in creating designer proteins for biomaterial applications.