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The protein-mineral interface in bone: a solid-state NMR study

Reference	BB/D013526/1
Principal Investigator / Supervisor	Professor Melinda Duer
Co-Investigators / Co-Supervisors	Dr Nigel Loveridge, Dr Rachel Murray
Institution	University of Cambridge
Department	Chemistry
Funding type	Research
Value (£)	195,476
Status	Completed
Type	Research Grant
Start date	02/05/2006
End date	01/05/2009
Duration	36 months

Abstract

Bone consists of a protein matrix (primarily collagen) in which are embedded crystals of a complex phase of calcium phosphate, dominated by hydroxyapatite. We will use solid-state NMR (primarily 31-P - 13-C REDOR) to identify the peptide groups in the matrix responsible for binding the matrix to the inorganic phase and to measure the distance of these groups from the crystal surfaces. The surface of the calcium phosphate crystals is known to be disordered, in common with the surface of most ionic crystals. We will use solid-state NMR to further characterise the structural units in the surface, via 31-P and 1-H NMR and various 2D correlation experiments. The work will use a variety of samples, including bone from animals of different ages and those suffering from osteoporosis and osteoarthritis, in order that we can determine the natural range of variation in the protein-mineral interface. In order to characterise the failure mode of the interface, and the stress required to disrupt it, samples will be mechanically impacted and re-examined by NMR.

Summary

Bone is a very important material in our bodies and those of other animals. It is known to consist of a matrix of protein (primarily, collagen) in which are embedded inorganic crystals of calcium phosphate. There is, at present, very little known about how the protein matrix and calcium phosphate crystals stick together, yet if they did not stick together in some way, the calcium phosphate crystals would all sink to the bottom of the bone and the bone would be floppy, and of very little use in supporting our bodies. The interface between the protein and calcium phosphate is thus of key importance in understanding how bone works as a material, how it is tough, and rigid enough to support our bodies and their movement, yet surprisingly resistant to fracture. We will use a measurement method called solid-state NMR to (a) identify which part of the protein matrix interacts with the calcium phosphate and (b) how far apart the matrix and crystals are. We will also look at how much force is required to break the link between the protein and calcium phosphate and see what effect diseases, such as osteoarthritis and osteoporosis have. The hope is that this will give clues as to how to treat these diseases as well as give us important information when building mathematical models to describe the functioning of bone as a material.

Committee	Closed Committee - Biomolecular Sciences (BMS)
Research Topics	Ageing, Structural Biology
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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