Regensburg 2013 – scientific programme
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BP: Fachverband Biologische Physik
BP 8: Posters: Proteins
BP 8.11: Poster
Monday, March 11, 2013, 17:30–19:30, Poster B2
Biophysical Characterization of the Platelet Factor 4-Heparin Complex Responsible for Heparin-induced Thrombocytopenia — •Martin Kreimann1, Werner Weitschies2, Andreas Greinacher3, and Mihaela Delcea1 — 1ZIK HIKE, University of Greifswald, Greifswald, Germany — 2Department of Biopharmaceutics and Pharmaceutical Technology, University of Greifswald, Greifswald, Germany — 3Institute for Immunology and Transfusion Medicine, University of Greifswald, Greifswald, Germany
The human protein Platelet Factor 4 is known to form complexes with the polysaccharide heparin when the latter is administered as an anticoagulant during cardiac surgery. This complex is responsible for the fatal adverse effect known as heparin-induced thrombocytopenia. The study of the PF4-heparin complex is primordial because heparin remains one of the most frequently used anticoagulants. To determine the biophysical basis of the PF4-heparin complexes, the binding interaction between PF4 and heparin was investigated by Isothermal Titration Calorimetry and Quartz Crystal Microbalance and the formed complexes were imaged by Atomic Force Microscopy. Our data shows that the binding of PF4 to heparin is mainly driven by electrostatic interactions. Hydrophobic interactions and conformational restrictions only play a minor role in the energetics of the process. AFM imaging shows that the height of PF4 molecules appearing as single features is reduced when complexed with heparin.