| Autor: |
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 |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
Nature Communications, Vol 15, Iss 1, Pp 1-15 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2041-1723 |
| DOI: |
10.1038/s41467-024-54309-8 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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