Platelet adhesion and aggregate formation controlled by immobilised and soluble VWF
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 casc...
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| Format: | Article |
| Language: | English |
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BMC
2020-09-01
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| Series: | BMC Molecular and Cell Biology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12860-020-00309-7 |
| _version_ | 1818275419723399168 |
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| author | Matthias F. Schneider Mohammad A. Fallah Christian Mess Tobias Obser Reinhard Schneppenheim Alfredo Alexander-Katz Stefan W. Schneider Volker Huck |
| author_facet | Matthias F. Schneider Mohammad A. Fallah Christian Mess Tobias Obser Reinhard Schneppenheim Alfredo Alexander-Katz Stefan W. Schneider Volker Huck |
| author_sort | Matthias F. Schneider |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T22:29:27Z |
| format | Article |
| id | doaj.art-4724211813a942f88ee1330187df5e2a |
| institution | Directory Open Access Journal |
| issn | 2661-8850 |
| language | English |
| last_indexed | 2024-12-12T22:29:27Z |
| publishDate | 2020-09-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Molecular and Cell Biology |
| spelling | doaj.art-4724211813a942f88ee1330187df5e2a2022-12-22T00:09:39ZengBMCBMC Molecular and Cell Biology2661-88502020-09-0121111310.1186/s12860-020-00309-7Platelet adhesion and aggregate formation controlled by immobilised and soluble VWFMatthias F. Schneider0Mohammad A. Fallah1Christian Mess2Tobias Obser3Reinhard Schneppenheim4Alfredo Alexander-Katz5Stefan W. Schneider6Volker Huck7Department of Physics, Medical and Biological Physics, Technical University DortmundDepartment of Chemistry, University of KonstanzUniversity Medical Centre Hamburg-EppendorfDepartment of Paediatric Haematology and Oncology, University Medical Centre Hamburg-EppendorfDepartment of Paediatric Haematology and Oncology, University Medical Centre Hamburg-EppendorfDepartment of Materials Science and Engineerin, Massachusetts Institute of TechnologyUniversity Medical Centre Hamburg-EppendorfUniversity Medical Centre Hamburg-EppendorfAbstract 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.http://link.springer.com/article/10.1186/s12860-020-00309-7Von Willebrand factorPlatelet adhesionShear activationPrimary haemostasis |
| spellingShingle | Matthias F. Schneider Mohammad A. Fallah Christian Mess Tobias Obser Reinhard Schneppenheim Alfredo Alexander-Katz Stefan W. Schneider Volker Huck Platelet adhesion and aggregate formation controlled by immobilised and soluble VWF BMC Molecular and Cell Biology Von Willebrand factor Platelet adhesion Shear activation Primary haemostasis |
| title | Platelet adhesion and aggregate formation controlled by immobilised and soluble VWF |
| title_full | Platelet adhesion and aggregate formation controlled by immobilised and soluble VWF |
| title_fullStr | Platelet adhesion and aggregate formation controlled by immobilised and soluble VWF |
| title_full_unstemmed | Platelet adhesion and aggregate formation controlled by immobilised and soluble VWF |
| title_short | Platelet adhesion and aggregate formation controlled by immobilised and soluble VWF |
| title_sort | platelet adhesion and aggregate formation controlled by immobilised and soluble vwf |
| topic | Von Willebrand factor Platelet adhesion Shear activation Primary haemostasis |
| url | http://link.springer.com/article/10.1186/s12860-020-00309-7 |
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