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Nat Mater. 2017 Feb;16(2):230-235. doi: 10.1038/nmat4772. Epub 2016 Oct 10.

Single-platelet nanomechanics measured by high-throughput cytometry.

Myers DR1,2,3,4,5, Qiu Y1,2,3,4,5, Fay ME1,2,3,4,5, Tennenbaum M6, Chester D7,8, Cuadrado J6, Sakurai Y1,2,3,4,5, Baek J1,2,3,4,5, Tran R1,2,3,4,5, Ciciliano JC1,3,4,5,9, Ahn B1,2,3,4,5, Mannino RG1,2,3,4,5, Bunting ST10, Bennett C1, Briones M1, Fernandez-Nieves A4,6, Smith ML11, Brown AC7,8, Sulchek T9, Lam WA1,2,3,4,5.

Author information

1
Department of Pediatrics, Division of Pediatric Hematology/Oncology, Aflac Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
2
The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology &Emory University, Atlanta, Georgia 30332, USA.
3
Winship Cancer Institute of Emory University, Atlanta, Georgia 30322, USA.
4
Parker H. Petit Institute of Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia 30332, USA.
5
Institute for Electronics and Nanotechnology, Georgia Institute of Technology, Atlanta, Georgia 30332, USA.
6
School of Physics, Georgia Institute of Technology, Atlanta, Georgia 30332, USA.
7
Joint Department of Biomedical Engineering, North Carolina State University and University of North Carolina at Chapel Hill, Raleigh, North Carolina 27695, USA.
8
Comparative Medicine Institute at North Carolina State University, Raleigh, North Carolina 27695, USA.
9
George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332, USA.
10
Department of Pathology, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
11
Department of Biomedical Engineering, Boston University, Boston, Massachusetts 02215, USA.

Abstract

Haemostasis occurs at sites of vascular injury, where flowing blood forms a clot, a dynamic and heterogeneous fibrin-based biomaterial. Paramount in the clot's capability to stem haemorrhage are its changing mechanical properties, the major drivers of which are the contractile forces exerted by platelets against the fibrin scaffold. However, how platelets transduce microenvironmental cues to mediate contraction and alter clot mechanics is unknown. This is clinically relevant, as overly softened and stiffened clots are associated with bleeding and thrombotic disorders. Here, we report a high-throughput hydrogel-based platelet-contraction cytometer that quantifies single-platelet contraction forces in different clot microenvironments. We also show that platelets, via the Rho/ROCK pathway, synergistically couple mechanical and biochemical inputs to mediate contraction. Moreover, highly contractile platelet subpopulations present in healthy controls are conspicuously absent in a subset of patients with undiagnosed bleeding disorders, and therefore may function as a clinical diagnostic biophysical biomarker.

PMID:
27723740
PMCID:
PMC5266633
DOI:
10.1038/nmat4772
[Indexed for MEDLINE]
Free PMC Article

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