Polyphosphates affect biological apatite nucleation

While biological apatite (bone mineral) resorption is understood, from the perspective of crystallization theory, nucleation is not. The degree of saturation (Ω) describes the chemical driving force for mineral dissolution (Ω <1) or formation (Ω > 1). Ω is the ratio of the ion activity product (IAP) of free apatite (available for reaction) component ion concentrations (predominately [Ca²⁺] and [PO¾⁻)] for apatite) and its solubility product (K(sp)). Free ion concentrations can be less than total ion concentrations if the ions form complexes, or if the ion speciation changes. Within the acidic bone resorption pit, free [PO¾⁻] is reduced due to speciation into H₂PO₄⁻. This reduces IAP(bio-Ap), and Ω(bio-Ap); at Ω(bio-Ap) <1, apatite dissolves. Apatite nucleation requires Ω(bio-Ap) >1, and bioaccumulation of molar total [Ca²⁺] and [PO¾⁻] to form the 60-70 weight percent mineral in bone tissue. This is possible with the polymerization of PO¾⁻ into polyphosphate [polyP: (PO₃⁻)(n)] which reduces free [PO¾⁻] while leaving total [P] unchanged. polyP forms neutral complexes by chelation with Ca²⁺, which further reduces free [Ca²⁺] and Ω(bio-Ap), yet total [Ca²⁺] is unchanged. In vitro experiments demonstrate reduction in free [Ca²⁺], free [PO¾⁻], and Ω(bio-Ap) by Ca-polyP formation, while total [Ca²⁺] and total [P] are constant. polyP depolymerization restores free [Ca²⁺] and [PO¾⁻] to total [Ca] and [P], and increases Ω(bio-Ap), favouring apatite nucleation.