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Abstract
Evidence is provided from studies on natural and artificial biofluids that the sequestration
of amorphous calcium phosphate by peptides or proteins to form nanocluster complexes
is of general importance in the control of physiological calcification. A naturally
occurring mixture of osteopontin peptides was shown, by light and neutron scattering,
to form calcium phosphate nanoclusters with a core-shell structure. In blood serum
and stimulated saliva, an invariant calcium phosphate ion activity product was found
which corresponds closely in form and magnitude to the ion activity product observed
in solutions of these osteopontin nanoclusters. This suggests that types of nanocluster
complexes are present in these biofluids as well as in milk. Precipitation of amorphous
calcium phosphate from artificial blood serum, urine and saliva was determined as
a function of pH and the concentration of osteopontin or casein phosphopeptides. The
position of the boundary between stability and precipitation was found to agree quantitatively
with the theory of nanocluster formation. Artificial biofluids were prepared that
closely matched their natural counterparts in calcium and phosphate concentrations,
pH, saturation, ionic strength and osmolality. Such fluids, stabilised by a low concentration
of sequestering phosphopeptides, were found to be highly stable and may have a number
of beneficial applications in medicine.