Differential surface activation of the A1 domain of von Willebrand factor

Citation

Tronic, E. H.; Yakovenko, O.; Weidner, T.; Baio, J. E.; Penkala, R.; Castner, D. G.; & Thomas, W. E. (2016). Differential surface activation of the A1 domain of von Willebrand factor. Biointerphases, 11(2), 029803. PMCID: 4788635

Abstract

The clotting protein von Willebrand factor (VWF) binds to platelet receptor glycoprotein Ibalpha (GPIbalpha) when VWF is activated by chemicals, high shear stress, or immobilization onto surfaces. Activation of VWF by surface immobilization is an important problem in the failure of cardiovascular implants, but is poorly understood. Here, the authors investigate whether some or all surfaces can activate VWF at least in part by affecting the orientation or conformation of the immobilized GPIbalpha-binding A1 domain of VWF. Platelets binding to A1 adsorbed onto polystyrene surfaces translocated rapidly at moderate and high flow, but detached at low flow, while platelets binding to A1 adsorbed onto glass or tissue-culture treated polystyrene surfaces translocated slowly, and detached only at high flow. Both x-ray photoelectron spectroscopy and conformation independent antibodies reported comparable A1 amounts on all surfaces. Time-of-flight secondary ion mass spectrometry (ToF-SIMS) and near-edge x-ray absorption fine structure spectra suggested differences in orientation on the three surfaces, but none that could explain the biological data. Instead, ToF-SIMS data and binding of conformation-dependent antibodies were consistent with the stabilization of an alternative more activated conformation of A1 by tissue culture polystyrene and especially glass. These studies demonstrate that different material surfaces differentially affect the conformation of adsorbed A1 domain and its biological activity. This is important when interpreting or designing in vitro experiments with surface-adsorbed A1 domain, and is also of likely relevance for blood-contacting biomaterials.

Keyword(s)

*Cell Adhesion
*Surface Properties
Blood Platelets/*physiology
glass
Humans
Platelet Glycoprotein GPIb-IX Complex/*metabolism
Polystyrenes
Protein Binding
Protein Structure, Tertiary
von Willebrand Factor/*metabolism

Notes

Tronic, Elaine H
Yakovenko, Olga
Weidner, Tobias
Baio, Joe E
Penkala, Rebecca
Castner, David G
Thomas, Wendy E
P41 EB002027/EB/NIBIB NIH HHS/
R01 HL106074/HL/NHLBI NIH HHS/
1R01 HL106074/HL/NHLBI NIH HHS/
EB-002027/EB/NIBIB NIH HHS/
Biointerphases. 2016 Jun 11;11(2):029803. doi: 10.1116/1.4943618.

Reference Type

Journal Article

Secondary Title

Biointerphases

Author(s)

Tronic, E. H.
Yakovenko, O.
Weidner, T.
Baio, J. E.
Penkala, R.
Castner, D. G.
Thomas, W. E.

Year Published

2016

Date Published

1749600000

Volume Number

11

Issue Number

2

ISSN/ISBN

1559-4106 (Electronic)
1559-4106 (Linking)

DOI

10.1116/1.4943618

PMCID

4788635