Hydrogels from Protein Engineering

Abstract

Protein-engineered hydrogels build upon the natural structure and function of proteins to create well-defined, multifunctional materials by cross-linking polypeptide chains together. Individual polypeptide chains are composed of independent peptide domains built from amino acid monomers. The engineered amino acid sequence is designed to form specific and reproducible structures of the selected peptide domains. The exact amino acid sequence of the polypeptide chain can be encoded into a DNA sequence, which is transfected into a host microorganism in order to produce a monodisperse batch of polypeptide chains. Interactions between individual polypeptide chains can be engineered to form hydrated macromolecular structures with tunable mechanical strength. These interchain interactions can include both noncovalent cross-linking between neighboring peptide domains as well as covalent cross-linking between amino acid residues to form stable hydrogels.In this chapter, we discuss the development of protein-engineered hydrogels with tunable mechanical and biochemical properties for biomaterial applications. First, we discuss the fundamentals of protein structure and recombinant protein synthesis. Next, we review the diversity of peptide domains that have been utilized in protein-engineered hydrogels to date, including cell-binding domains, structural domains, and molecular recognition domains. We continue to describe the various enzymatic and synthetic chemistry strategies that have been utilized to create covalently cross-linked protein-engineered hydrogels. We conclude with an in-depth discussion of cellular interactions with protein-engineered hydrogels and of the ability to tune the biomechanics and biochemistry of the materials to direct cellular phenotype.Development of novel protein-engineered hydrogels for therapeutic applications requires regulation of specific cellular behavior through tuning of the structural, mechanical, and biochemical properties of the hydrogel. The cellular response and activation of intracellular signaling pathways for cell adhesion and migration is different between traditional two-dimensional (2D) cell culture environments and native three-dimensional (3D) cell environments, thus the use of 3D materials for Biomimetic Approaches for Biomaterials Development, First Edition. Edited by João F. Mano.