Effects of Confinement and Molecular Regulation on Biomineralization

Abstract:

Bone is a composite material with unique properties. These biologically important properties depend on the carefully regulated growth of hydroxyapatite crystal within the collagen matrix. Type I collagen is the most abundant protein in the bone matrix, making up about 90-95% of the organic material. Collagen self-assembles, allowing for gaps or hole zones to form between fibrils. Within these hole zones as well as along the fibrils is where inorganic hydroxyapatite bone mineral begins to form. We call this process biomineralization. Non-collagenous proteins in the bone matrix control the growth of this mineral. Fetuin is an example of one of these regulatory proteins that inhibits mineral growth and formation. This regulation and the proteins involved have been primarily studied in dilute aqueous solution, however, the real bone matrix is a highly crowded environment (collagen, hole zones, fibrils, etc.). We know that the structure and function of these proteins in addition to the mineralization process is affected by molecular confinement or crowding, we just aren’t sure to what extent. Within this project, we are investigating the effects that crowding has on the structure of fetuin and on the mineralization process in vitro. We are collecting mineral and analyzing it via IR spectroscopy, TEM, and electron diffraction. If the structure and function of mineral inhibitors such as fetuin does change, this could be explained by variation in the crystal structure and phase that we analyze at the end of each experiment. This research is important, because proper bone mineralization allows our bones to stand apart from all other materials. Without proper regulation of this process, mineralization will either be excessive or deficient which could compromise the quality of bone tissue and lead to fractures and breaks.