I. Singh, E. Themistou, L. Porcar and S. Neelamegham, Biophys J . 96(6):2313-20, 2009.

1. Shear rate 3000/s 0/s Time (hr) q 0.6nm neutron beam VWF sheared in quartz couette cell 0 3 1 Control of protein structure and function by hydrodynamic shearS. Neelamegham1, I. Singh1, E.Themistou1, L. Porcar21SUNY Buffalo, 2NIST DMR-0454672 NIH - HL76211 • Can fluid shear alter the structure of proteins? To address this question, we applied fluid shear stress to the largest protein in blood, Von Willebrand Factor (VWF), and studied changes in protein conformation using the CHRNS small angle neutron scattering (SANS) instrument and fluorescence spectroscopy. Changes in VWF structure were measured in real-time using SANS (Figure at right). These data show prominent changes in VWF scattering at length scales <10nm (scattering vector (q) range >0.6/nm) when the applied shear rate was  3000/s. Fluorescence spectroscopy and the environment sensitive dye bis-ANS were used to study VWF conformation at higher shear rates, up to 9600/s. These studies reveal that hydrophobic pockets within VWF are exposed upon shearing the protein at shear rates  6000/s. Changes in VWF conformation reported here likely regulate protein function in blood circulation. I. Singh, E.Themistou, L. Porcar and S. Neelamegham, Biophys J. 96(6):2313-20, 2009.