Transient particle tracking microrheology of plasma coagulation via the intrinsic pathway
The maintenance of hemostasis to ensure vascular integrity is dependent upon the rapid conversion of zymogen species of the coagulation cascade to their enzymatically active forms. This process culminates in the generation of the serine protease thrombin and polymerization of fibrin to prevent vascu...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
De Gruyter
2023-04-01
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| Series: | Applied Rheology |
| Subjects: | |
| Online Access: | https://doi.org/10.1515/arh-2022-0129 |
| _version_ | 1797832463230173184 |
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| author | Mao Yating Tan Mingyang Kohs Tia C. L. Sylman Joanna L. Ngo Anh T. P. Puy Cristina McCarty Owen J. T. Walker Travis W. |
| author_facet | Mao Yating Tan Mingyang Kohs Tia C. L. Sylman Joanna L. Ngo Anh T. P. Puy Cristina McCarty Owen J. T. Walker Travis W. |
| author_sort | Mao Yating |
| collection | DOAJ |
| description | The maintenance of hemostasis to ensure vascular integrity is dependent upon the rapid conversion of zymogen species of the coagulation cascade to their enzymatically active forms. This process culminates in the generation of the serine protease thrombin and polymerization of fibrin to prevent vascular leak at sites of endothelial cell injury or loss of cellular junctions. Thrombin generation can be initiated by the extrinsic pathway of coagulation through exposure of blood to tissue factor at sites of vascular damage, or alternatively by the coagulation factor (F) XII activated by foreign surfaces with negative charges, such as glass, through the contact activation pathway. Here, we used transient particle tracking microrheology to investigate the mechanical properties of fibrin in response to thrombin generation downstream of both coagulation pathways. We found that the structural heterogeneity of fibrin formation was dependent on the reaction kinetics of thrombin generation. Pharmacological inhibition of FXII activity prolonged the time to form fibrin and increased the degree of heterogeneity of fibrin, resulting in fibrin clots with reduced mechanical properties. Taken together, this study demonstrates a dependency of the physical biology of fibrin formation on activation of the contact pathway of coagulation. |
| first_indexed | 2024-04-09T14:09:21Z |
| format | Article |
| id | doaj.art-f6ca618cdfb548ae94a2ca8f5d84a88a |
| institution | Directory Open Access Journal |
| issn | 1617-8106 |
| language | English |
| last_indexed | 2024-04-09T14:09:21Z |
| publishDate | 2023-04-01 |
| publisher | De Gruyter |
| record_format | Article |
| series | Applied Rheology |
| spelling | doaj.art-f6ca618cdfb548ae94a2ca8f5d84a88a2023-05-06T15:58:54ZengDe GruyterApplied Rheology1617-81062023-04-013313263610.1515/arh-2022-0129Transient particle tracking microrheology of plasma coagulation via the intrinsic pathwayMao Yating0Tan Mingyang1Kohs Tia C. L.2Sylman Joanna L.3Ngo Anh T. P.4Puy Cristina5McCarty Owen J. T.6Walker Travis W.7Department of Chemical and Biomedical Engineering, FAMU-FSU College of Engineering, FLorida State University, Tallahassee, FL, USAInstitute of Materials Science, University of Connecticut, Storrs, CT, USABiomedical Engineering, School of Medicine, ORegon Health and Science University, Portland, OR, USABiomedical Engineering, School of Medicine, ORegon Health and Science University, Portland, OR, USABiomedical Engineering, School of Medicine, ORegon Health and Science University, Portland, OR, USABiomedical Engineering, School of Medicine, ORegon Health and Science University, Portland, OR, USABiomedical Engineering, School of Medicine, ORegon Health and Science University, Portland, OR, USAChemical and Biological Engineering, South Dakota School of Mines & Technology, Rapid City, SD, USAThe maintenance of hemostasis to ensure vascular integrity is dependent upon the rapid conversion of zymogen species of the coagulation cascade to their enzymatically active forms. This process culminates in the generation of the serine protease thrombin and polymerization of fibrin to prevent vascular leak at sites of endothelial cell injury or loss of cellular junctions. Thrombin generation can be initiated by the extrinsic pathway of coagulation through exposure of blood to tissue factor at sites of vascular damage, or alternatively by the coagulation factor (F) XII activated by foreign surfaces with negative charges, such as glass, through the contact activation pathway. Here, we used transient particle tracking microrheology to investigate the mechanical properties of fibrin in response to thrombin generation downstream of both coagulation pathways. We found that the structural heterogeneity of fibrin formation was dependent on the reaction kinetics of thrombin generation. Pharmacological inhibition of FXII activity prolonged the time to form fibrin and increased the degree of heterogeneity of fibrin, resulting in fibrin clots with reduced mechanical properties. Taken together, this study demonstrates a dependency of the physical biology of fibrin formation on activation of the contact pathway of coagulation.https://doi.org/10.1515/arh-2022-0129microrheologycoagulationheterogeneity |
| spellingShingle | Mao Yating Tan Mingyang Kohs Tia C. L. Sylman Joanna L. Ngo Anh T. P. Puy Cristina McCarty Owen J. T. Walker Travis W. Transient particle tracking microrheology of plasma coagulation via the intrinsic pathway Applied Rheology microrheology coagulation heterogeneity |
| title | Transient particle tracking microrheology of plasma coagulation via the intrinsic pathway |
| title_full | Transient particle tracking microrheology of plasma coagulation via the intrinsic pathway |
| title_fullStr | Transient particle tracking microrheology of plasma coagulation via the intrinsic pathway |
| title_full_unstemmed | Transient particle tracking microrheology of plasma coagulation via the intrinsic pathway |
| title_short | Transient particle tracking microrheology of plasma coagulation via the intrinsic pathway |
| title_sort | transient particle tracking microrheology of plasma coagulation via the intrinsic pathway |
| topic | microrheology coagulation heterogeneity |
| url | https://doi.org/10.1515/arh-2022-0129 |
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