The blood protein von Willebrand Factor (vWF) is critical to the initiation of blood clotting after vascular injury in humans and other mammals. From a molecular scale perspective, a single vWF protein is enormous: one protein is comprised of hundreds of thousands to multiple millions of atoms. Fully unfolded, the string-like proteins can reach lengths up to 10 microns - larger than a tiny speck of dust. Yet they instead spend much of their existence circulating through our bloodstream in tightly balled-up globular shapes. Upon injury, blood flow near the cut causes the proteins to unfold, revealing binding sites all along their length. This permits vWF to bind with platelets in our blood and collagen exposed on injured blood vessel walls, initiating blood clotting.
We're using advanced simulation methods, closely coupled to microfluidic visualization and single molecule force spectroscopy experiments, to reveal the details of how this fascinating protein works. In doing so, we hope to help improve diagnosis and clinical treatment of the nearly 2% of the human population that suffers from vWF-related bleeding disorders. We also believe understanding vWF response in varying flow conditions can inform future efforts to synthesize molecular systems that mimic vWF's response for other applications.
Below: Weighted ensemble statistical sampling methods, coupled with molecular scale dynamic simulations, have allowed our group to reveal the rate of vWF protein unfolding in rates of blood flow that are far below what could previously be studied, and yet are highly relevant to vWF's function in the human body.
This research was an interdisciplinary collaborative project at Lehigh co-led by four engineering professors: Edmund Webb (Mechanical Engineering & Mechanics), Frank Zhang (Bioengineering), Alparslan Oztekin (Mechanical Engineering & Mechanics) and Xhuanhong Cheng (Materials Science & Engineering, Bioengineering).
Read more about flow-induced unraveling of polymers including pathological unfolding of von Willebrand factor and how protein-glycan interactions can prevent mechanical unfolding.