Autoantibodies immuno-mechanically modulate platelet contractile force and bleeding risk

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 () and David R. Myers ()
Additional contact information
Oluwamayokun Oshinowo: Georgia Institute of Technology and Emory University
Renee Copeland: Georgia Institute of Technology and Emory University
Anamika Patel: Emory University
Nina Shaver: Georgia Institute of Technology and Emory University
Meredith E. Fay: Georgia Institute of Technology and Emory University
Rebecca Jeltuhin: Georgia Institute of Technology and Emory University
Yijin Xiang: Emory University
Christina Caruso: Emory University
Adiya E. Otumala: Georgia Institute of Technology and Emory University
Sarah Hernandez: Emory University
Priscilla Delgado: Georgia Institute of Technology and Emory University
Gabrielle Dean: Children’s Healthcare of Atlanta
James M. Kelvin: Georgia Institute of Technology and Emory University
Daniel Chester: Chapel Hill and North Carolina State University
Ashley C. Brown: Chapel Hill and North Carolina State University
Erik C. Dreaden: Georgia Institute of Technology and Emory University
Traci Leong: Emory University
Jesse Waggoner: Chapel Hill and North Carolina State University
Renhao Li: Emory University
Eric Ortlund: Emory University
Carolyn Bennett: Emory University
Wilbur A. Lam: Georgia Institute of Technology and Emory University
David R. Myers: Georgia Institute of Technology and Emory University

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: 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.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-54309-8 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-54309-8

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-54309-8

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().