Directing polymorph specific calcium carbonate formation with de novo protein templates

Biomolecules modulate inorganic crystallization to generate hierarchically structured biominerals1-5, but the atomic structure of the organic-inorganic interfaces that regulate mineralization remain unknown6-8. We hypothesized that heterogeneous nucleation of calcium carbonate could be achieved by a structured flat molecular template that pre-organizes calcium ions on its surface. To test this hypothesis, we designed helical repeat proteins (DHRs) displaying regularly spaced carboxylate arrays on their surfaces and found that both protein monomers and protein-Ca2+ assemblies directly nucleate nano-calcite with non-natural (110) or (202) faces while vaterite, which forms first absent the proteins, is bypassed. The nanocrystals then assemble by oriented attachment into calcite mesocrystals. We find further that nanocrystal size and polymorph can be tuned by varying the length and surface chemistry of the designed protein templates. Thus, bio-mineralization can be programmed using de novo protein design, providing a route to next-generation hybrid materials. One sentence summaryDe novo designed protein templates promote nucleation of nano-calcite and direct its growth by oriented particle attachment.