Biomimetic Peptides Controlling Prenucleation Species: probing mineralization regulation in biomineralization

• Applicant: Privatdozent Dr. Stephan E. Wolf
• Subject Area: Physical Chemistry of Molecules, Liquids and Interfaces, Biophysical Chemistry ; Analytical Chemistry ; Biological and Biomimetic Chemistry
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 568846534

Biomineralizing organisms convert mineral deposits, like calcium carbonate (CaC) or phosphate (CaP), into complex multifunctional solids with functionality performances unmatched by current synthetic approaches. Typically, biosynthesis bypasses classical, ion-mediated crystallization and enforces a nonclassical route governed by amorphous precursors whose structural features dictate the final biomineral properties. It is unsettled which molecular mechanisms allow organisms to exert such sophisticated control over a forming amorphous phase. However, studies showed that synthetic molecules impact amorphous mineral formation if binding to prenucleation species (PNS), stable poly-ionic solute species that are essential drivers of nonclassical schemes of CaC and CaP. Moreover, biomineral-associated proteins, known to enforce transient precursors, feature uncommon chemical motifs (e.g., rich in acidic low-complexity repeat units or post-translational modifications). This research project combines these recent findings and will assess whether these unique protein motifs act as PNS binding sites. The project will anatomize the pre- and post-nucleation stage of model peptide-mineral systems by employing binding assays, in situ potentiometry, spectroscopy, and diffraction. For probing the relevant peptide-PNS complexes, magic angle spinning (MAS) nuclear magnetic resonance (NMR) spectroscopy would be the method of choice. However, in situ MAS NMR is infeasible for aqueous systems due to the difficulty of fast-rotating liquids under MAS and the information loss induced by motional averaging. We will overcome this obstacle by a unique approach using cryofixation of NMR samples: freeze-quench vitrifies the aqueous dispersion, immobilizing and preserving the fragile peptide-PNS assemblies. Via this novel approach, low-temperature MAS NMR becomes feasible and will reveal the molecular interactions behind the stabilization of PNS by identified peptide motifs, further supported by DFT simulation. This project employs a multi-methodological, cross-scale approach across scales, synergizing on the complementarity expertise of the involved partners to understanding of how organisms shift a mineral system away from crystallization towards self-assembly and nonclassical processes.

• DFG Programme: Research Grants
• International Connection: France
• Cooperation Partner: Professor Dr. Thierry Azais