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Investigating von Willebrand Factor Pathophysiology Using a Flow Chamber Model of von Willebrand Factor-platelet String Formation
Published on: August 14, 2017
Exponential size distribution of von Willebrand factor
Svenja Lippok1, Tobias Obser, Jochen P Müller
1Faculty of Physics and Center for NanoScience, Ludwig Maximilian University, Munich, Germany.
Biophysical Journal
|September 10, 2013
Summary
Von Willebrand Factor (VWF) size distribution follows an exponential decay, reflecting its polymerization. This distribution is altered by mutations and the protease ADAMTS13, offering potential clinical insights.
Area of Science:
- Biophysics
- Biochemistry
- Hematology
Background:
- Von Willebrand Factor (VWF) is essential for blood clotting and acts as a mechanosensor.
- VWF multimer size is critical for its function under shear flow.
- Understanding VWF size distribution is key to diagnosing related bleeding disorders.
Purpose of the Study:
- To quantify the size distribution of recombinant and native Von Willebrand Factor (VWF).
- To investigate the impact of mutations and proteases on VWF size.
- To establish VWF size distribution as a potential clinical biomarker.
Main Methods:
- Multilateral approach combining quantitative gel electrophoresis, fluorescence correlation spectroscopy (FCS), and total internal reflection fluorescence microscopy (TIRFM).
- Analysis of recombinant VWF, VWF-eGFP, and VWF from blood samples.
- Computer simulation of VWF cleavage by ADAMTS13.
Main Results:
- VWF multimer size distribution exhibits an exponential decay, consistent with step-growth polymerization.
- The polymerization extent, described by this distribution, is reduced in the VWF-IIC mutant.
- ADAMTS13 protease shifts the VWF size distribution towards smaller sizes, a process quantifiable by FCS and simulations.
Conclusions:
- VWF size distribution can be accurately described by an exponential decay model.
- This quantitative assessment provides valuable biophysical characterization of VWF.
- VWF size distribution analysis holds potential as a diagnostic indicator for clinical applications.
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