Structural investigations of VWF under flow by FTIR spectroscopy

本文旨在对诱导和控制剪切流作用下的vWF结构塑性进行FTIR光谱分析。vWF是触发原发性止血的机械感蛋白。该方法是基于多学科设计的表面声波（SAW）驱动的流动电池装置。这将使在最原生的环境中对vWF进行详细的结构分析成为可能。将分析聚合物全长多域vWF配合物和单功能域vWF配合物。流动装置的至少一个表面将是可功能化的。因此，在可调剪切流中特定固定vWF结构域或结合伙伴将用于结合研究。进一步分析vWF与ADAMTS13（一种具有血小板反应蛋白1型基元的崩解素和金属蛋白酶，成员13）的酶切关系，将获得有关止血调节的结构信息。

This proposal aims at the FTIR spectroscopic analysis of Von Willebrand Factor (vWF) structural plasticity under induced and controlled shear flow. vWF is the mechanosensoric protein which triggers primary hemostasis. The approach is based on the multidisciplinary design of a surface acoustic wave (SAW) driven flow cell device. This will enable the in detail structural analysis of vWF in a most native environment. Both polymeric full length, multidomain vWF complexes and single, functional domains will be analyzed. At least one surface of the flow device will be functionalizable. Thus, a specific immobilization of a vWF domain or a binding partner within adjustable shear flow will be used for binding studies. Further analysis of the enzymatic vWF cleavage with ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) will give structural information about hemostasis regulation.