De novo design of protein-mineral complexes

Abstract

Biomineralization is the process by which living organisms create functional hybrid materials, including shells, bones, teeth, and magnetosomes. These biominerals exhibit enhanced properties in aspects such as fracture toughness, mechanical resilience, and hierarchical structural organization compared to pure mineral counterparts. Understanding the molecular mechanisms of biomineralization, particularly how proteins assemble at solid-liquid interfaces, and mimicking these processes in the laboratory could one day lead to the development of novel hybrid materials with impactful applications ranging from carbon sinks for climate change mitigation to microelectronics. A significant barrier in biomineralization research is that the natural proteins involved are frequently unstructured, heterogeneous, or insoluble, complicating their structural characterization and engineering. To overcome this, de novo protein design provides a powerful strategy for creating tailored proteins with precise structures and functions. Within the Baker lab, de novo proteins have been successfully engineered to interface with minerals. These designed proteins can guide the nucleation, growth, and polymorph of mineral crystals. We further engineer these protein-mineral interfaces to self-assemble into complex higher-order structures, including two-dimensional sheets, cages, or fibers, bringing us closer to macroscopic material composites.