Fetuin-A is a mineral carrier protein: small angle neutron scattering provides new insight on Fetuin-A controlled calcification inhibition

Biophys J. 2010 Dec 15;99(12):3986-95. doi: 10.1016/j.bpj.2010.10.030.


Clinical studies and animal experiments have shown that the serum protein fetuin-A is a highly effective inhibitor of soft tissue calcification. This inhibition mechanism was elucidated on the basis of an in vitro fetuin-A-mineral model system. In a previous study, we found that in a two-stage process ∼100-nm sized calciprotein particles (CPPs) were formed whose final stage was stabilized by a compact outer fetuin-A monolayer against further growth. Quantitative small-angle neutron scattering data analysis revealed that even at a fetuin-A concentration close to the stability limit, only approximately one-half of the mineral ions and only 5% of the fetuin-A were contained in the CPPs. To uncover the interplay of the remaining supersaturated mineral ion fraction and of the 95% non-CPP fetuin-A, we explored the fetuin-A monomer fraction in solution by contrast variation small-angle neutron scattering. Our results suggest that the mineral ions coalesce to subnanometer-sized clusters, reminiscent of Posner clusters, which are stabilized by fetuin-A monomers. Hence, our experiments revealed a second mechanism of long-term mineral ion stabilization by the fetuin-A that is complementary to the formation of CPPs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcification, Physiologic*
  • Calcium / metabolism
  • Calcium Phosphates / metabolism
  • Carrier Proteins / metabolism*
  • Cattle
  • Colloids
  • Minerals / metabolism*
  • Neutron Diffraction*
  • Protein Binding
  • Scattering, Small Angle*
  • Time Factors
  • Ultrafiltration
  • alpha-Fetoproteins / metabolism*


  • Calcium Phosphates
  • Carrier Proteins
  • Colloids
  • Minerals
  • alpha-Fetoproteins
  • Calcium