Platelet adhesion and aggregate formation controlled by immobilised and soluble VWF
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12860_2020_Article_309.pdf
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Author(s)
Schneider, Matthias F.
Fallah, Mohammad A.
Mess, Christian
Obser, Tobias
Schneppenheim, Reinhard
Alexander-Katz, Alfredo
Schneider, Stefan W.
Huck, Volker
Date Issued
September 2020
Journal
BMC Molecular and Cell Biology
Publisher
Springer Science and Business Media LLC
Citation
Schneider, Matthias F. et al. "Platelet adhesion and aggregate formation controlled by immobilised and soluble VWF." BMC Molecular and Cell Biology 21, 1 (September 2020): 64 © 2020 The Authors
Version
Final published version
Abstract
Background
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.
Results
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.
Conclusions
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.
MIT Department
Massachusetts Institute of Technology. Department of Materials Science and Engineering
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DOI of Published Version
https://doi.org/10.1186/s12860-020-00309-7
