Force generation in human blood platelets by filamentous actomyosin structures

Blood platelets are central elements of the blood clotting response after wounding. Upon vessel damage, they bind to the surrounding matrix and contract the forming thrombus, thus helping to restore normal blood circulation. The hemostatic function of platelets is directly connected to their mechani...

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Main Authors: Zelená, Anna (Author) , Blumberg, Johannes (Author) , Probst, Dimitri (Author) , Gerasimaitė, Rūta (Author) , Lukinavičius, Gražvydas (Author) , Schwarz, Ulrich S. (Author) , Köster, Sarah (Author)
Format: Article (Journal)
Language:English
Published: 22 August 2023
In: Biophysical journal
Year: 2023, Volume: 122, Issue: 16, Pages: 3340-3353
ISSN:1542-0086
DOI:10.1016/j.bpj.2023.07.010
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.bpj.2023.07.010
Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S0006349523004617
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Author Notes:Anna Zelená, Johannes Blumberg, Dimitri Probst, Rūta Gerasimaitė, Gražvydas Lukinavičius, Ulrich S. Schwarz, and Sarah Köster

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520 |a Blood platelets are central elements of the blood clotting response after wounding. Upon vessel damage, they bind to the surrounding matrix and contract the forming thrombus, thus helping to restore normal blood circulation. The hemostatic function of platelets is directly connected to their mechanics and cytoskeletal organization. The reorganization of the platelet cytoskeleton during spreading occurs within minutes and leads to the formation of contractile actomyosin bundles, but it is not known if there is a direct correlation between the emerging actin structures and the force field that is exerted to the environment. In this study, we combine fluorescence imaging of the actin structures with simultaneous traction force measurements in a time-resolved manner. In addition, we image the final states with superresolution microscopy. We find that both the force fields and the cell shapes have clear geometrical patterns defined by stress fibers. Force generation is localized in a few hotspots, which appear early during spreading, and, in the mature state, anchor stress fibers in focal adhesions. Moreover, we show that, for a gel stiffness in the physiological range, force generation is a very robust mechanism and we observe no systematic dependence on the amount of added thrombin in solution or fibrinogen coverage on the substrate, suggesting that force generation after platelet activation is a threshold phenomenon that ensures reliable thrombus contraction in diverse environments. 
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