Intermolecular channels direct crystal orientation in mineralized collagen

Abstract

The mineralized collagen fibril is the basic building block of bone, and is commonly pictured as a parallel array of ultrathin carbonated hydroxyapatite (HAp) platelets distributed throughout the collagen. This orientation is often attributed to an epitaxial relationship between the HAp and collagen molecules inside 2D voids within the fibril. Although recent studies have questioned this model, the structural relationship between the collagen matrix and HAp, and the mechanisms by which collagen directs mineralization remain unclear. Here, we use XRD to reveal that the voids in the collagen are in fact cylindrical pores with diameters of ~2 nm, while electron microscopy shows that the HAp crystals in bone are only uniaxially oriented with respect to the collagen. From in vitro mineralization studies with HAp, CaCO3 and γ-FeOOH we conclude that confinement within these pores, together with the anisotropic growth of HAp, dictates the orientation of HAp crystals within the collagen fibril.

Collagen Structure-Function Mapping Informs Applications for Regenerative Medicine

“…Alternatively, several acidic non-collagenous bone phosphoproteins (e.g., SIBLING proteins such as osteopontin, bone sialoprotein, and phosphophoryn) are proposed to associate with collagen to provide the mineralization substrate [ 12 , 37 ]. Finally, it has been proposed that the spaces within and between the microfibrils may support biomineralization without the need for mineralization nucleation sequences or collagen-associated proteins [ 38 , 39 , 40 , 41 ].…”

Matrix Vesicles: Role in Bone Mineralization and Potential Use as Therapeutics

“…Osteoblasts are responsible for the creation of the mineralized organic matrix. They produce collagen type 1, which is considered to be the template for mineral nucleation and mineral crystal growth [3][4][5]. After mineral precursors have entered the collagen gap region, hydroxyapatite crystals grow outside the dimensions of the fibril, forming an interconnected continuous cross-fibrillar pattern [6].…”

Percolation networks inside 3D model of the mineralized collagen fibril

“…A widely accepted model of the 3D arrangement of apatite minerals within the MCF assumes that in the longitudinal direction mineral crystals are disposed in a staggered arrangement, while parallel layers of apatite span the equatorial plane of the fibril 14 . According to 15 , 16 , the architecture of the collagen phase as an ordered matrix contributes to the co-alignment between the crystallographic c-axis of apatite and the longitudinal axis of collagen fibril with an angular distribution of ± 20 degrees 15 , 17 .…”

“…From tomographic data 2 , 16 it emerged also the evidence that the mineral phase is present as individual crystallites and as aggregates. Recent investigations of Xu et al 16 at the length scale of a single fibril identified, on average, small stacks of 2–4 platelets from the analysis of 300 nm long MCF with a diameter of 100 nm, that corresponds to approximately 150 platelets. Conversely, in areas with higher mineral density, larger groups of roughly 8 platelets were individuated 16 .…”

“…Recent investigations of Xu et al 16 at the length scale of a single fibril identified, on average, small stacks of 2–4 platelets from the analysis of 300 nm long MCF with a diameter of 100 nm, that corresponds to approximately 150 platelets. Conversely, in areas with higher mineral density, larger groups of roughly 8 platelets were individuated 16 . Landis et al 17 suggested that apatite crystal fusion can influence the biomechanical properties of bone.…”