Protein-Based Engineered Living Materials: From Programmable Self-Assembly to Mechanical Reinforcement via Biomineralization

Abstract The convergence of synthetic biology and materials science has given rise to the field of engineered living materials (ELMs). ELMs move beyond inert biomaterials by incorporating genetically programmable cells that can sense, adapt, and respond to their environment. Designing ELMs requires consideration of both the genetic tractability and physiology of the cellular chassis and the synergies with the surrounding scaffold that houses them. To that end, protein-based scaffolds inspired by structural proteins such as curli, elastin, silk, and collagen provide a supportive environment for living cells due to their tunable mechanical properties, biocompatibility, and functionalization potential through fused bioactive domains. A hurdle for advancing ELMs from proof-of-concept systems to robust materials is their typical soft nature, which prevents their deployment in mechanically demanding engineering applications. Here too, protein-based scaffolds offer a promising avenue to enhance the stiffness, strength, and durability of ELMs by fusing structural proteins to biomineralizing peptides, an approach inspired by how nature forms some of its hardest biological structures, including diatom frustules, mollusk shells, and bone. In this review, we discuss design principles for the manufacture of mechanically robust protein-based ELMs. We first cover aspects related to the cellular components, focusing on their physiological properties and secretion capabilities. We then turn to recombinant protein-based scaffolds, discussing first building blocks inspired by natural structural proteins (e.g., silk-like, elastin-like, and curli) as well as fusions thereof or to biomineralization peptides. Overall, our aim is to discuss promising routes for advancing ELMs from proof-of-concept systems to robust materials suitable for real-world use.