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Titanium preferential binding sites in human serum transferrin at physiological concentrations.

Yoana Nuevo-Ordoñez1, M Montes-Bayón, E Blanco González

  • 1Department of Physical and Analytical Chemistry, Faculty of Chemistry, University of Oviedo, Oviedo, Spain.

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Titanium (Ti) in patients with intramedullary nails binds to serum transferrin (Tf) specifically in the N-lobe. This binding occurs in vivo and is unaffected by sialic acid levels, suggesting a cellular entry pathway for titanium.

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Area of Science:

  • Biochemistry
  • Metalloprotein Chemistry
  • Biomaterials Science

Background:

  • Serum transferrin (Tf) is crucial for iron metabolism, binding iron and other metal ions.
  • Titanium (Ti) is used in intramedullary nails, and its binding to Tf in vivo is poorly understood.
  • Previous studies show Tf binds Ti tightly in vitro, but physiological relevance is unclear.

Purpose of the Study:

  • To investigate the in vivo chemical association of titanium to serum transferrin in patients with intramedullary titanium nails.
  • To determine the specific binding site of titanium on transferrin.
  • To explore the influence of sialic acid on titanium-transferrin binding.

Main Methods:

  • Elemental mass spectrometry using double focusing inductively coupled plasma (DF-ICP-MS) for detection.
  • Chromatographic separation techniques with varying gradient conditions to analyze Ti/Fe-Tf forms.
  • Neuraminidase (sialidase) incubation to assess the role of sialic acid in Tf.

Main Results:

  • Titanium in human serum from patients with intramedullary nails is uniquely associated with the N-lobe of transferrin.
  • Titanium binding affinity to transferrin remains similar for both native and monosialylated Tf.
  • Binding of Ti to Tf occurs specifically in the N-lobe, irrespective of sialic acid content.

Conclusions:

  • In vivo titanium from implants uniquely binds to the N-lobe of serum transferrin.
  • Sialic acid content does not significantly affect titanium binding to transferrin.
  • The Fe(C)Ti(N)-Tf complex may facilitate cellular titanium uptake via transferrin receptors.