Combined computational modeling and experimental study of the biomechanical mechanisms of platelet-driven contraction of fibrin clots
Abstract While blood clot formation has been relatively well studied, little is known about the mechanisms underlying the subsequent structural and mechanical clot remodeling called contraction or retraction. Impairment of the clot contraction process is associated with both life-threatening bleedin...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-08-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-023-05240-z |
| _version_ | 1797557144539627520 |
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| author | Christian Michael Francesco Pancaldi Samuel Britton Oleg V. Kim Alina D. Peshkova Khoi Vo Zhiliang Xu Rustem I. Litvinov John W. Weisel Mark Alber |
| author_facet | Christian Michael Francesco Pancaldi Samuel Britton Oleg V. Kim Alina D. Peshkova Khoi Vo Zhiliang Xu Rustem I. Litvinov John W. Weisel Mark Alber |
| author_sort | Christian Michael |
| collection | DOAJ |
| description | Abstract While blood clot formation has been relatively well studied, little is known about the mechanisms underlying the subsequent structural and mechanical clot remodeling called contraction or retraction. Impairment of the clot contraction process is associated with both life-threatening bleeding and thrombotic conditions, such as ischemic stroke, venous thromboembolism, and others. Recently, blood clot contraction was observed to be hindered in patients with COVID-19. A three-dimensional multiscale computational model is developed and used to quantify biomechanical mechanisms of the kinetics of clot contraction driven by platelet-fibrin pulling interactions. These results provide important biological insights into contraction of platelet filopodia, the mechanically active thin protrusions of the plasma membrane, described previously as performing mostly a sensory function. The biomechanical mechanisms and modeling approach described can potentially apply to studying other systems in which cells are embedded in a filamentous network and exert forces on the extracellular matrix modulated by the substrate stiffness. |
| first_indexed | 2024-03-10T17:13:11Z |
| format | Article |
| id | doaj.art-66f585ef44854295b748b4e146d8d9c7 |
| institution | Directory Open Access Journal |
| issn | 2399-3642 |
| language | English |
| last_indexed | 2024-03-10T17:13:11Z |
| publishDate | 2023-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj.art-66f585ef44854295b748b4e146d8d9c72023-11-20T10:34:40ZengNature PortfolioCommunications Biology2399-36422023-08-016111610.1038/s42003-023-05240-zCombined computational modeling and experimental study of the biomechanical mechanisms of platelet-driven contraction of fibrin clotsChristian Michael0Francesco Pancaldi1Samuel Britton2Oleg V. Kim3Alina D. Peshkova4Khoi Vo5Zhiliang Xu6Rustem I. Litvinov7John W. Weisel8Mark Alber9Department of Mathematics, University of California RiversideDepartment of Mathematics, University of California RiversideDepartment of Mathematics, University of California RiversideDepartment of Cell and Developmental Biology, University of Pennsylvania School of MedicineDepartment of Pharmacology, University of Pennsylvania School of MedicineDepartment of Mathematics, University of California RiversideDepartment of Applied and Computational Mathematics and Statistics, University of Notre DameDepartment of Cell and Developmental Biology, University of Pennsylvania School of MedicineDepartment of Cell and Developmental Biology, University of Pennsylvania School of MedicineDepartment of Mathematics, University of California RiversideAbstract While blood clot formation has been relatively well studied, little is known about the mechanisms underlying the subsequent structural and mechanical clot remodeling called contraction or retraction. Impairment of the clot contraction process is associated with both life-threatening bleeding and thrombotic conditions, such as ischemic stroke, venous thromboembolism, and others. Recently, blood clot contraction was observed to be hindered in patients with COVID-19. A three-dimensional multiscale computational model is developed and used to quantify biomechanical mechanisms of the kinetics of clot contraction driven by platelet-fibrin pulling interactions. These results provide important biological insights into contraction of platelet filopodia, the mechanically active thin protrusions of the plasma membrane, described previously as performing mostly a sensory function. The biomechanical mechanisms and modeling approach described can potentially apply to studying other systems in which cells are embedded in a filamentous network and exert forces on the extracellular matrix modulated by the substrate stiffness.https://doi.org/10.1038/s42003-023-05240-z |
| spellingShingle | Christian Michael Francesco Pancaldi Samuel Britton Oleg V. Kim Alina D. Peshkova Khoi Vo Zhiliang Xu Rustem I. Litvinov John W. Weisel Mark Alber Combined computational modeling and experimental study of the biomechanical mechanisms of platelet-driven contraction of fibrin clots Communications Biology |
| title | Combined computational modeling and experimental study of the biomechanical mechanisms of platelet-driven contraction of fibrin clots |
| title_full | Combined computational modeling and experimental study of the biomechanical mechanisms of platelet-driven contraction of fibrin clots |
| title_fullStr | Combined computational modeling and experimental study of the biomechanical mechanisms of platelet-driven contraction of fibrin clots |
| title_full_unstemmed | Combined computational modeling and experimental study of the biomechanical mechanisms of platelet-driven contraction of fibrin clots |
| title_short | Combined computational modeling and experimental study of the biomechanical mechanisms of platelet-driven contraction of fibrin clots |
| title_sort | combined computational modeling and experimental study of the biomechanical mechanisms of platelet driven contraction of fibrin clots |
| url | https://doi.org/10.1038/s42003-023-05240-z |
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