Abstract
This study presents an investigation into the role of Osteocalcin (OC) on bone biomechanics, with the results demonstrating that the protein’s α-helix structures play a critical role in energy dissipation behavior in healthy conditions. In the first instance, α-helix structures have high affinity with the Hydroxyapatite (HAp) mineral surface and provide favorable conditions for adsorption of OC proteins onto the mineral surface. Using steered molecular dynamics simulation, several key energy dissipation mechanisms associated with α-helix structures were observed, which included stick–slip behavior, a sacrificial bond mechanism and a favorable binding feature provided by the Ca2+ motif on the OC protein. In the case of Type-2 Diabetes, this study demonstrated that possible glycation of the OC protein can occur through covalent crosslinking between Arginine and N-terminus regions, causing disruption of α-helices leading to a lower protein affinity to the HAp surface. Furthermore, the loss of α-helix structures allowed protein deformation to occur more easily during pulling and key energy dissipation mechanisms observed in the healthy configuration were no longer present. This study has significant implications for our understanding of bone biomechanics, revealing several novel mechanisms in OC’s involvement in energy dissipation. Furthermore, these mechanisms can be disrupted following the onset of Type-2 Diabetes, implying that glycation of OC could have a substantial contribution to the increased bone fragility observed during this disease state.
Highlights
This study presents an investigation into the role of Osteocalcin (OC) on bone biomechanics, with the results demonstrating that the protein’s α-helix structures play a critical role in energy dissipation behavior in healthy conditions
This study considers the full 49-residue polypeptide representation of OC and uses this to explore the effect of glycation on the overall energy dissipation potential, providing novel insight into how OC protein mechanics are altered during T2 Diabetes
A Steered Molecular Dynamics (SMD) model was used to simulate OC protein pulling from mineral surface to evaluate energy dissipation
Summary
This study presents an investigation into the role of Osteocalcin (OC) on bone biomechanics, with the results demonstrating that the protein’s α-helix structures play a critical role in energy dissipation behavior in healthy conditions. Bone is a naturally occurring composite material that consists of hydroxyapatite (HAp) mineral crystals and an organic matrix, which is comprised of both collagenous and non-collagenous proteins These component phases are hierarchically organised to provide a highly optimised structure that exhibits a multitude of intricate toughening mechanisms that contribute to the tissue’s excellent fracture resistance[1,2,3,4,5,6]. Several studies have established that these non-collagenous protein complexes facilitate plastic sacrificial sliding, which appears to be a major contributor to the tissue’s excellent fracture toughness[13,14,15] This mechanism manifests at higher length scales in the form of voids that correspond to dilatational bands, which dissipate energy during discrete fracture e vents[11] and enable regions of diffuse damage to form under fatigue loading r egimes[16]. The effect of glycation on the mechanical role of OC has not been investigated
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