Catching platelets from the bloodflow: the role of the conformation of von Willebrand factor

Belyaev, Aleksey V.

doi:10.1051/mmnp/2018043

Cited by 11 publications

(20 citation statements)

References 49 publications

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“…Griffin et al try to find new anti-thrombotic drugs in the form of nanoparticles that reduce the amount of uncoiling of vWF at high shear rates [31]. Additionally, Belyaev modelled the binding of platelets and vWF [32]. Furthermore, experimentalists try to understand the behaviour of the vWF better by designing experiments that specifically target high shear rate regimes [5,12].…”

Section: Introductionmentioning

confidence: 99%

Identifying the start of a platelet aggregate by the shear rate and the cell-depleted layer

Rooij

Závodszky

Tarksalooyeh

et al. 2019

J. R. Soc. Interface.

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Computer simulations were performed to study the transport of red blood cells and platelets in high shear flows, mimicking earlier published in vitro experiments in microfluidic devices with high affinity for platelet aggregate formation. The goal is to understand and predict where thrombus formation starts. Additionally, the need of cell-based modelling in these microfluidic devices is demonstrated by comparing our results with macroscopic models, wherein blood is modelled as a continuous fluid. Hemocell, a cell-based blood flow simulation framework is used to investigate the transport physics in the microfluidic devices. The simulations show an enlarged cell-depleted layer at the site where a platelet aggregate forms in the experiments. In this enlarged cell-depleted layer, the probability to find a platelet is higher than in the rest of the microfluidic device. In addition, the shear rates are sufficiently high to allow for the von Willebrand factor to elongate in this region. We hypothesize that the enlarged cell-depleted layer combined with a sufficiently large platelet flux and sufficiently high shear rates result in an haemodynamic environment that is a preferred location for initial platelet aggregation.

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Section: Introductionmentioning

confidence: 99%

Identifying the start of a platelet aggregate by the shear rate and the cell-depleted layer

Rooij

Závodszky

Tarksalooyeh

et al. 2019

J. R. Soc. Interface.

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“…One may extrapolate this observation on the vWf multimers: for longer chains the mechanical load on A2 domain is more resemblant to the directional pulling. This is especially pronounced for the grafted multimers, which usually experience greater local tension as compared to the free-flowing ones [12,72]. We also see that under a higher shear stress the extension of the A2 domain has a tendency to follow the complete unfolding pathway, rather than the reassembly pathway, so that the probability for the correct ADAMTS13-vWf complex formation is higher.…”

Section: The Three Domains A1a2a3: the Unfolding Of A2 In Shear Flowmentioning

confidence: 79%

Exposure of Von Willebrand Factor Cleavage Site in A1A2A3-Fragment under Extreme Hydrodynamic Shear

et al. 2021

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Von Willebrand Factor (vWf) is a giant multimeric extracellular blood plasma involved in hemostasis. In this work we present multi-scale simulations of its three-domains fragment A1A2A3. These three domains are essential for the functional regulation of vWf. Namely the A2 domain hosts the site where the protease ADAMTS13 cleavages the multimeric vWf allowing for its length control that prevents thrombotic conditions. The exposure of the cleavage site follows the elongation/unfolding of the domain that is caused by an increased shear stress in blood. By deploying Lattice Boltzmann molecular dynamics simulations based on the OPEP coarse-grained model for proteins, we investigated at molecular level the unfolding of the A2 domain under the action of a perturbing shear flow. We described the structural steps of this unfolding that mainly concerns the β-strand structures of the domain, and we compared the process occurring under shear with that produced by the action of a directional pulling force, a typical condition of single molecule experiments. We observe, that under the action of shear flow, the competition among the elongational and rotational components of the fluid field leads to a complex behaviour of the domain, where elongated structures can be followed by partially collapsed melted globule structures with a very different degree of exposure of the cleavage site. Our simulations pose the base for the development of a multi-scale in-silico description of vWf dynamics and functionality in physiological conditions, including high resolution details for molecular relevant events, e.g., the binding to platelets and collagen during coagulation or thrombosis.

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“…The PyOIF has been further used by external research groups for evaluation of VAD rotatory blood pumps [ 54 ], for analysis of micro-roughness and its consequences for platelets activation and platelet catching [ 55 , 56 ], for simulation of magnetic active polymers for versatile microfluidic devices [ 57 ]. Recently, the PyOIF module has been used to investigate the equilibrium structure and quasi-static deformational response of a magnetic polymersome, a hollow object whose magnetoactive part is its shell [ 58 ].…”

Section: Resultsmentioning

confidence: 99%

PyOIF: Computational tool for modelling of multi-cell flows in complex geometries

et al. 2020

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A user ready, well documented software package PyOIF contains an implementation of a robust validated computational model for cell flow modelling. The software is capable of simulating processes involving biological cells immersed in a fluid. The examples of such processes are flows in microfluidic channels with numerous applications such as cell sorting, rare cell isolation or flow fractionation. Besides the typical usage of such computational model in the design process of microfluidic devices, PyOIF has been used in the computer-aided discovery involving mechanical properties of cell membranes. With this software, single cell, many cell, as well as dense cell suspensions can be simulated. Many cell simulations include cell-cell interactions and analyse their effect on the cells. PyOIF can be used to test the influence of mechanical properties of the membrane in flows and in membrane-membrane interactions. Dense suspensions may be used to study the effect of cell volume fraction on macroscopic phenomena such as cell-free layer, apparent suspension viscosity or cell degradation. The PyOIF module is based on the official ESPResSo distribution with few modifications and is available under the terms of the GNU General Public Licence. PyOIF is based on Python objects representing the cells and on the C++ computational core for fluid and interaction dynamics. The source code is freely available at GitHub repository, runs natively under Linux and MacOS and can be used in Windows Subsystem for Linux. The communication among PyOIF users and developers is maintained using active mailing lists. This work provides a basic background to the underlying computational models and to the implementation of interactions within this framework. We provide the prospective PyOIF users with a practical example of simulation script with reference to our publicly available User Guide.

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Catching platelets from the bloodflow: the role of the conformation of von Willebrand factor

Cited by 11 publications

References 49 publications

Identifying the start of a platelet aggregate by the shear rate and the cell-depleted layer

Identifying the start of a platelet aggregate by the shear rate and the cell-depleted layer

Exposure of Von Willebrand Factor Cleavage Site in A1A2A3-Fragment under Extreme Hydrodynamic Shear

PyOIF: Computational tool for modelling of multi-cell flows in complex geometries

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