A bio-inspired method for direct measurement of local wall shear rates with micrometer localization using the multimeric protein von Willebrand factor as sensor molecule

Abstract

Wall shear rates are critical for a broad variety of fluidic phenomena and are taken into account in nearly every experimental or simulation study. Generally, shear rates are not observable directly but rather derived from other parameters such as pressure and flow, often assuming somehow idealized systems. However, there is a biological system which is able to constantly measure the wall shear as a part of a regulatory circuit: The blood circulation system takes advantage of shear rate sensor (protein)molecules (multimeric forms of von Willebrand Factor, VWF), which are dissolved in the blood plasma and dramatically change their conformation under shear conditions. The conformational changes are accompanied by several functional variations and therefore interplay with the regulation of the coagulation system. In this study, we use a recombinantly produced and therefore well-defined multimeric form of VWF as a sensor which directly responds to shear rates. Shear rates, up to 32.000 s, were obtained using a kind of micro-plate-to-plate rheometer capable of adsorbing shear-stretched VWF oligomeric molecules on a surface to conserve their differently stretched conformation and so allow detection of their elongation by atomic force microscopy. The laminar flow in this geometrically simple device has been characterized by adopting classical fluid dynamical models, in order to ensure well-known, stable shear rates which could be correlated quantitatively with an observed stretching of sensor molecules.

The role of ultralarge multimers in recombinant human von Willebrand factor – a review of physico-and biochemical studies and findings in in vivo models and in humans with von Willebrand disease

“…Almost im-tion of the proteolytic cleavage process of VWF by ADAMTS13 (17). A recently developed method could even be utilized to visualize conformational changes of rVWF and its shear dependent protein-protein interactions on the macro-molecular level (18). In a study in which rVWF was compared with a pdVWF preparation, individual molecules with a broad size distribution in terms of covalently linked monomeric units were distinguishable in pdVWF, reflecting the heterogeneous character of this protein (19).…”

Shear-Induced Extensional Response Behaviors of Tethered von Willebrand Factor

“…Previous authors have used single-molecule experiments and simulations to examine the flow-induced dynamics and functionality of tethered and free-flowing VWF, which helped elucidate molecular-level behaviors crucial to VWF biology and physics (19,21). Atomic force microscopy (AFM) has been used to capture in situ variations in the three-dimensional structure of VWF under shearing (26,46). However, the temporal resolution of AFM is insufficient for capturing the highly dynamic behavior of VWF in flow.…”