title: Spatially and temporally controlled biomineralization is facilitated by interaction between self-assembled dentin matrix protein 1 and calcium phosphate nuclei in solution.
abstract: Bone and dentin biomineralization are well-regulated processes mediated by extracellular matrix proteins. It is widely believed that specific matrix proteins in these tissues modulate nucleation of apatite nanoparticles and their growth into micrometer-sized crystals via molecular recognition at the protein-mineral interface. However, this assumption has been supported only circumstantially, and the exact mechanism remains unknown. Dentin matrix protein 1 (DMP1) is an acidic matrix protein, present in the mineralized matrix of bone and dentin. In this study, we have demonstrated using synchrotron small-angle X-ray scattering that DMP1 in solution can undergo oligomerization and temporarily stabilize the newly formed calcium phosphate nanoparticle precursors by sequestering them and preventing their further aggregation and precipitation. The solution structure represents the first low-resolution structural information for DMP1. Atomic force microscopy and transmission electron microscopy studies further confirmed that the nascent calcium phosphate nuclei formed in solution were assembled into ordered protein-mineral complexes with the aid of oligomerized DMP1, recombinant and native. This study reveals a novel mechanism by which DMP1 might facilitate initiation of mineral nucleation at specific sites during bone and dentin mineralization and prevent spontaneous calcium phosphate precipitation in areas in which mineralization is not desirable.
authors.affiliation: Department of Oral Biology, University of Illinois, Chicago, Illinois 60612, USA.
authors.forename: Gen
authors.initials: G
authors.lastname: He
authors.forename: Sivakumar
authors.initials: S
authors.lastname: Gajjeraman
authors.forename: David
authors.initials: D
authors.lastname: Schultz
authors.forename: David
authors.initials: D
authors.lastname: Cookson
authors.forename: Chunlin
authors.initials: C
authors.lastname: Qin
authors.forename: William T
authors.initials: WT
authors.lastname: Butler
authors.forename: Jianjun
authors.initials: J
authors.lastname: Hao
authors.forename: Anne
authors.initials: A
authors.lastname: George
mesh_terms: D002113:Calcification, Physiologic; D002130:Calcium Phosphates / Q000737:chemistry*; D016326:Extracellular Matrix Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D018625:Microscopy, Atomic Force; D010750:Phosphoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012996:Solutions / Q000737:chemistry*; D017356:Synchrotrons; D014965:X-Rays
chemical_list: D002130:Calcium Phosphates; D016326:Extracellular Matrix Proteins; D010750:Phosphoproteins; D011994:Recombinant Proteins; D012996:Solutions; C020243:calcium phosphate