Autoantibodies immuno-mechanically modulate platelet contractile force and bleeding risk
Abstract Altered mechanotransduction has been proposed as a putative mechanism for disease pathophysiology, yet evidence remains scarce. Here we introduce a concept we call single cell immuno-mechanical modulation, which links immunology, integrin biology, cellular mechanics, and disease pathophysio...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-11-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-54309-8 |
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| author | Oluwamayokun Oshinowo Renee Copeland Anamika Patel Nina Shaver Meredith E. Fay Rebecca Jeltuhin Yijin Xiang Christina Caruso Adiya E. Otumala Sarah Hernandez Priscilla Delgado Gabrielle Dean James M. Kelvin Daniel Chester Ashley C. Brown Erik C. Dreaden Traci Leong Jesse Waggoner Renhao Li Eric Ortlund Carolyn Bennett Wilbur A. Lam David R. Myers |
| author_facet | Oluwamayokun Oshinowo Renee Copeland Anamika Patel Nina Shaver Meredith E. Fay Rebecca Jeltuhin Yijin Xiang Christina Caruso Adiya E. Otumala Sarah Hernandez Priscilla Delgado Gabrielle Dean James M. Kelvin Daniel Chester Ashley C. Brown Erik C. Dreaden Traci Leong Jesse Waggoner Renhao Li Eric Ortlund Carolyn Bennett Wilbur A. Lam David R. Myers |
| author_sort | Oluwamayokun Oshinowo |
| collection | DOAJ |
| description | Abstract Altered mechanotransduction has been proposed as a putative mechanism for disease pathophysiology, yet evidence remains scarce. Here we introduce a concept we call single cell immuno-mechanical modulation, which links immunology, integrin biology, cellular mechanics, and disease pathophysiology and symptomology. Using a micropatterned hydrogel-laden coverslip compatible with standard fluorescence microscopy, we conduct a clinical mechanobiology study, specifically focusing on immune thrombocytopenia (ITP), an autoantibody-mediated platelet disorder that currently lacks a reliable biomarker for bleeding risk. We discover that in pediatric ITP patients (n = 53), low single platelet contraction force alone is a “physics-based” biomarker of bleeding (92.3% sensitivity, 90% specificity). Mechanistically, autoantibodies and monoclonal antibodies drive increases and decreases of cell force by stabilizing integrins in different conformations depending on the targeted epitope. Hence, immuno-mechanical modulation demonstrates how antibodies may pathologically alter mechanotransduction to cause clinical symptoms and this phenomenon can be leveraged to control cellular mechanics for research, diagnostic, and therapeutic purposes. |
| format | Article |
| id | doaj-art-40f51aedd93b469eb32c5e6e52882d4a |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-40f51aedd93b469eb32c5e6e52882d4a2024-12-01T12:33:05ZengNature PortfolioNature Communications2041-17232024-11-0115111510.1038/s41467-024-54309-8Autoantibodies immuno-mechanically modulate platelet contractile force and bleeding riskOluwamayokun Oshinowo0Renee Copeland1Anamika Patel2Nina Shaver3Meredith E. Fay4Rebecca Jeltuhin5Yijin Xiang6Christina Caruso7Adiya E. Otumala8Sarah Hernandez9Priscilla Delgado10Gabrielle Dean11James M. Kelvin12Daniel Chester13Ashley C. Brown14Erik C. Dreaden15Traci Leong16Jesse Waggoner17Renhao Li18Eric Ortlund19Carolyn Bennett20Wilbur A. Lam21David R. Myers22The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory UniversityThe Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory UniversityDepartment of Biochemistry, Emory University School of Medicine, Emory UniversityThe Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory UniversityThe Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory UniversityThe Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory UniversityDepartment of Pediatrics, Aflac Cancer Center and Blood Disorders Service, Children’s Healthcare of Atlanta, Emory University School of Medicine, Emory UniversityDepartment of Pediatrics, Aflac Cancer Center and Blood Disorders Service, Children’s Healthcare of Atlanta, Emory University School of Medicine, Emory UniversityThe Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory UniversityDepartment of Medicine, Division of Infectious Diseases, Emory UniversityThe Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory UniversityAflac Cancer Center and Blood Disorders Service, Children’s Healthcare of AtlantaThe Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory UniversityJoint Department of Biomedical Engineering of University of North Carolina, Chapel Hill and North Carolina State UniversityJoint Department of Biomedical Engineering of University of North Carolina, Chapel Hill and North Carolina State UniversityThe Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory UniversityDepartment of Biostatistics & Bioinformatics, Rollins School of Public Health, Emory UniversityJoint Department of Biomedical Engineering of University of North Carolina, Chapel Hill and North Carolina State UniversityDepartment of Pediatrics, Aflac Cancer Center and Blood Disorders Service, Children’s Healthcare of Atlanta, Emory University School of Medicine, Emory UniversityDepartment of Biochemistry, Emory University School of Medicine, Emory UniversityDepartment of Pediatrics, Aflac Cancer Center and Blood Disorders Service, Children’s Healthcare of Atlanta, Emory University School of Medicine, Emory UniversityThe Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory UniversityThe Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory UniversityAbstract Altered mechanotransduction has been proposed as a putative mechanism for disease pathophysiology, yet evidence remains scarce. Here we introduce a concept we call single cell immuno-mechanical modulation, which links immunology, integrin biology, cellular mechanics, and disease pathophysiology and symptomology. Using a micropatterned hydrogel-laden coverslip compatible with standard fluorescence microscopy, we conduct a clinical mechanobiology study, specifically focusing on immune thrombocytopenia (ITP), an autoantibody-mediated platelet disorder that currently lacks a reliable biomarker for bleeding risk. We discover that in pediatric ITP patients (n = 53), low single platelet contraction force alone is a “physics-based” biomarker of bleeding (92.3% sensitivity, 90% specificity). Mechanistically, autoantibodies and monoclonal antibodies drive increases and decreases of cell force by stabilizing integrins in different conformations depending on the targeted epitope. Hence, immuno-mechanical modulation demonstrates how antibodies may pathologically alter mechanotransduction to cause clinical symptoms and this phenomenon can be leveraged to control cellular mechanics for research, diagnostic, and therapeutic purposes.https://doi.org/10.1038/s41467-024-54309-8 |
| spellingShingle | Oluwamayokun Oshinowo Renee Copeland Anamika Patel Nina Shaver Meredith E. Fay Rebecca Jeltuhin Yijin Xiang Christina Caruso Adiya E. Otumala Sarah Hernandez Priscilla Delgado Gabrielle Dean James M. Kelvin Daniel Chester Ashley C. Brown Erik C. Dreaden Traci Leong Jesse Waggoner Renhao Li Eric Ortlund Carolyn Bennett Wilbur A. Lam David R. Myers Autoantibodies immuno-mechanically modulate platelet contractile force and bleeding risk Nature Communications |
| title | Autoantibodies immuno-mechanically modulate platelet contractile force and bleeding risk |
| title_full | Autoantibodies immuno-mechanically modulate platelet contractile force and bleeding risk |
| title_fullStr | Autoantibodies immuno-mechanically modulate platelet contractile force and bleeding risk |
| title_full_unstemmed | Autoantibodies immuno-mechanically modulate platelet contractile force and bleeding risk |
| title_short | Autoantibodies immuno-mechanically modulate platelet contractile force and bleeding risk |
| title_sort | autoantibodies immuno mechanically modulate platelet contractile force and bleeding risk |
| url | https://doi.org/10.1038/s41467-024-54309-8 |
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