Platelet adhesion and aggregate formation controlled by immobilised and soluble VWF
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 V...
| Main Authors: | , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
Springer Science and Business Media LLC
2020
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| Online Access: | https://hdl.handle.net/1721.1/127675 |
| _version_ | 1811098050043576320 |
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| author | Schneider, Matthias F. Fallah, Mohammad A. Mess, Christian Obser, Tobias Schneppenheim, Reinhard Alexander-Katz, Alfredo Schneider, Stefan W. Huck, Volker |
| author2 | Massachusetts Institute of Technology. Department of Materials Science and Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Materials Science and Engineering Schneider, Matthias F. Fallah, Mohammad A. Mess, Christian Obser, Tobias Schneppenheim, Reinhard Alexander-Katz, Alfredo Schneider, Stefan W. Huck, Volker |
| author_sort | Schneider, Matthias F. |
| collection | MIT |
| description | 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 | 2024-09-23T17:09:11Z |
| format | Article |
| id | mit-1721.1/127675 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T17:09:11Z |
| publishDate | 2020 |
| publisher | Springer Science and Business Media LLC |
| record_format | dspace |
| spelling | mit-1721.1/1276752022-09-30T00:02:07Z Platelet adhesion and aggregate formation controlled by immobilised and soluble VWF Schneider, Matthias F. Fallah, Mohammad A. Mess, Christian Obser, Tobias Schneppenheim, Reinhard Alexander-Katz, Alfredo Schneider, Stefan W. Huck, Volker Massachusetts Institute of Technology. Department of Materials Science and Engineering 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. 2020-09-22T15:08:43Z 2020-09-22T15:08:43Z 2020-09 2020-02 2020-09-13T03:15:14Z Article http://purl.org/eprint/type/JournalArticle 2661-8850 https://hdl.handle.net/1721.1/127675 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 en http://dx.doi.org/10.1186/s12860-020-00309-7 BMC Molecular and Cell Biology Creative Commons Attribution https://creativecommons.org/licenses/by/4.0/ The Author(s) application/pdf Springer Science and Business Media LLC BioMed Central |
| spellingShingle | Schneider, Matthias F. Fallah, Mohammad A. Mess, Christian Obser, Tobias Schneppenheim, Reinhard Alexander-Katz, Alfredo Schneider, Stefan W. Huck, Volker Platelet adhesion and aggregate formation controlled by immobilised and soluble VWF |
| 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 |
| url | https://hdl.handle.net/1721.1/127675 |
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