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Nanostrukturen und Grenzflächen Vortrag: Mi., 18:00–18:20 M-V22
Inhibition of Calcium Phosphate Formation in the Presence of the Protein
Fetuin-A
Alexander Heiss 2 , Hitoshi Endo 1 , Willi Jahnen-Dechent 2 ,
Dietmar Schwahn 1
1 IFF - FZ Jülich, 52425 Jülich – 2 IZKF BioMAT, Universitätsklinik, Pauwelsstrasse
30, 52074 Aachen
Fetuin-A / α2-HS glycoprotein is a liver derived serum protein [1]. It strongly accumulates
in bone due to its affinity for the mineral phase[2] and a direct impact on
bone metabolism was reported [3]. However, the prime physiological role of fetuin-A
apparently is the systemic inhibition of calcium phosphate mineral deposition in extracellular
fluids [4]. Clinical studies conducted in humans demonstrated that reduced
fetuin-A serum levels in dialysis patients correlate with the extent of soft tissue calcification
and mortality [5]. Thus the lack of fetuin-A has serious pathobiochemical
consequences. SANS is a rather new experimental technique in this field of biomineralization,
it delivers detailed structural information about mineral-protein composites
by applying contrast variation method which is done by proper varying the H2O/D2O
composition of the aqueous solution [6].
The formation and maturation of the mineral particles in the presence of fetuin proceeds
in a two-stage process. During the first stage particles of about 250 ˚A radius of
gyration were observed for about 5 hours immediately after mixing. Between 5 and
10 hours the particles slowly increased their size to the order of 500 ˚A representing the
second stage. From 10 to 24 hours (the experimental endpoint) we observed stable
particles.
The structure of the mineral-organic particles of the second stage was further analyzed
by the method of contrast variation [6]. The partial scattering functions were
derived by the “singular value decomposition” method. The self-term PP,P represents
a bimodal distribution of the fetuin-A attributed to the mineralized particles (at low
Q) and the fetuin-A monomers (at high Q). All self-terms show Porods Q −4 power law
indicating compact particles with a sharp interphase. The positive cross-term PP,M
suggests a mineral core covered by a protein layer. We found an octacalcium phosphate
core and a dense protein monolayer, which protects the mineral from further growth
until sedimentation takes place. So, inhibition of mineral deposition is based on the
stabilization of 1000 ˚A sized colloidal particles.
We thank German Science Foundation for financial support within the priority program
“Principles of Biomineralization”.
[1] K.O. Pedersen, Nature 3914 (1944) 575. [2] J.T. Triffitt et al., Nature 262 (1976)
226. [3] M. Szweras et al., J. Biol. Chem. 277 (2002) 1999. [4] C. Schäfer et al., J. Clin.
Invest. 112 (2003) 357. [5] M. Ketteler et al., Lancet 361 (2003) 828. [6] H. Endo, D.
Schwahn , H. Cölfen, J. Chem. Phys. 120 (2004) 9410.