Platelet adhesion and aggregate formation controlled by immobilised and soluble VWF

It has been demonstrated that von Willebrand factor (VWF) mediated platelet-endothelium and platelet-platelet interactions are shear dependent. The VWF's mobility under dynamic conditions (e.g. flow) is pivotal to platelet adhesion and VWF-mediated aggregate formation in the cascade of VWF-plat...

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Bibliographic Details
Published in:BMC cell biology 2020-09, Vol.21 (1), p.1-64, Article 64
Main Authors: Schneider, Matthias F, Fallah, Mohammad A, Mess, Christian, Obser, Tobias, Schneppenheim, Reinhard, Alexander-Katz, Alfredo, Schneider, Stefan W, Huck, Volker
Format: Article
Language:English
Subjects:
Aggregates
Biopolymers
Blood platelets
Cell adhesion
Endothelium
Glycoproteins
Health aspects
Investigations
Macromolecules
Microfluidics
Mutation
Physiological aspects
Physiology
Platelet adhesion
Platelets
Primary haemostasis
Protein research
Protein-protein interactions
Shear activation
Structure
Von Willebrand factor
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Summary:It has been demonstrated that von Willebrand factor (VWF) mediated platelet-endothelium and platelet-platelet interactions are shear dependent. The VWF's mobility under dynamic conditions (e.g. flow) is pivotal to platelet adhesion and VWF-mediated aggregate formation in the cascade of VWF-platelet interactions in haemostasis. Combining microfluidic tools with fluorescence and reflection interference contrast microscopy (RICM), here we show, that specific deletions in the A-domains of the biopolymer VWF affect both, adhesion and aggregation properties independently. Intuitively, the deletion of the A1-domain led to a significant decrease in both adhesion and aggregate formation of platelets. Nevertheless, the deletion of the A2-domain revealed a completely different picture, with a significant increase in formation of rolling aggregates (gain of function). We predict that the A2-domain effectively 'masks' the potential between the platelet glycoprotein (GP) Ib and the VWF A1-domain. Furthermore, the deletion of the A3-domain led to no significant variation in either of the two functional characteristics. These data demonstrate that the macroscopic functional properties i.e. adhesion and aggregate formation cannot simply be assigned to the properties of one particular domain, but have to be explained by cooperative phenomena. The absence or presence of molecular entities likewise affects the properties (thermodynamic phenomenology) of its neighbours, therefore altering the macromolecular function.
ISSN:2661-8850
2661-8850
1471-2121
DOI:10.1186/s12860-020-00309-7