Platelet adhesion and aggregate formation controlled by immobilised and soluble VWF
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(2020) 21:64
BMC Molecular and Cell Biology
RESEARCH ARTICLE
Open Access
Platelet adhesion and aggregate formation controlled by immobilised and soluble VWF Matthias F. Schneider1†, Mohammad A. Fallah2†, Christian Mess3, Tobias Obser4, Reinhard Schneppenheim4, Alfredo Alexander-Katz5, Stefan W. Schneider3 and Volker Huck3,6*
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. Keywords: Von Willebrand factor, Platelet adhesion, Shear activation, Primary haemostasis
Background The shear dependent role of von Willebrand factor (VWF) during primary haemostasis is very well established and investigated [1–10]. Understanding the VWF function is consisted of the physical aspects of hydrodynamics and structural conformations, and physiological aspects
* Correspondence: [email protected] † Matthias F. Schneider and Mohammad A. Fallah contributed equally to this work. 3 University Medical Centre Hamburg-Eppendorf, Centre for Internal Medicine, Martinistr. 52, 20246 Hamburg, Germany 6 Heidelberg University, Medical Faculty Mannheim, Experimental Dermatology, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany Full list of author information is available at the end of the article
ranging from the underlying molecular biology to its functional characteristics and clinical impact. Clinically, both qualitative (Type II) and quantitative (Type I and III) VWF variants are classified in the framework of von Willebrand disease (VWD) [11–13]. VWD as a hereditary disease is a common bleeding disorder caused by mutations of VWF resulting in deficiency
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