title: Fetuin-A is a mineral carrier protein: small angle neutron scattering provides new insight on Fetuin-A controlled calcification inhibition.
abstract: 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.
authors.affiliation: Institute of Solid State Research, Helmholtz Research Center Jülich, Jülich, Germany. alexander.heiss@post.rwth-aachen.de
authors.forename: Alexander
authors.initials: A
authors.lastname: Heiss
authors.forename: Vitaliy
authors.initials: V
authors.lastname: Pipich
authors.forename: Willi
authors.initials: W
authors.lastname: Jahnen-Dechent
authors.forename: Dietmar
authors.initials: D
authors.lastname: Schwahn
mesh_terms: D000818:Animals; D002113:Calcification, Physiologic; D002118:Calcium / Q000378:metabolism; D002130:Calcium Phosphates / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D002417:Cattle; D003102:Colloids; D008903:Minerals / Q000378:metabolism*; D033363:Neutron Diffraction; D011485:Protein Binding; D053838:Scattering, Small Angle; D013997:Time Factors; D014462:Ultrafiltration; D000509:alpha-Fetoproteins / Q000378:metabolism*
chemical_list: D002130:Calcium Phosphates; D002352:Carrier Proteins; D003102:Colloids; D008903:Minerals; D000509:alpha-Fetoproteins; D002118:Calcium