Biogenesis of hard tissue – the growth and development of mineral structures in and/or around an organism – is a process that is largely controlled by proteins. Tooth enamel, and bone are examples of highly specialized materials that exist naturally due to underlying protein-mediated mechanisms. Understanding mechanistic details surrounding the structure-function relationship of these proteins has been the white whale for engineers trying to mimic these processes for the design of new, bioinspired materials. The salivary protein statherin is known to control the biomineralization of hydroxyapatite (HAP), the main component of teeth and bone and has been studied extensively in the past. At the same time, experimental studies providing mechanistic insight at the molecular level have been lacking. We here determined the secondary structure and orientation of statherin at HAP surfaces <i>in situ</i> using sum frequency generation (SFG) spectroscopy and molecular dynamics simulations. By combining both methods via theoretical calculations we determined the orientation and secondary structure of statherin at the HAP surface. The figure shows a cartoon schematic of statherin. The analysis shows that the binding domain (green in the figure) is ordered and structured while the C-terminal (grey in the figure), unbound part remains mobile and mostly unstructured. Focusing further on the 15-residue binding domain by comparing experimental spectra for the binding domain in isolation with SFG spectra calculated from extensive metadynamics datasets using a novel algorithm, we gain new insight into the complex mechanism by which statherin controls HAP surfaces.

Binding structure of the human salivary protein statherin on hydroxyapatite determined by sum frequency generation spectroscopy and molecular dynamics simulations

ACS Spring Meeting 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.