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Author Notes:

Corresponding Author: Wilbur A. Lam, Address: 2015 Uppergate Dr, NE; Emory Children’s Center - Room 448; Atlanta, GA 30322, wilbur.lam@emory.edu, Phone: 404-727-7473, Fax: 404-727-4455.

See publication for full list of author contributions.

The authors wish to thank Andrew Shaw of the Parker H. Petit Institute for Bioengineering and Bioscience at the Georgia Institute of Technology (GT); Neil Anthony and the Emory University Integrated Cellular Imaging Microscopy Core of the Children’s Pediatric Research Center; and the GT Institute for Electronics and Nanotechnology (IEN) cleanroom.

The authors declare no competing financial interests.

Subject:

Research Funding:

Financial support provided by NIH R01 (HL121264), NIH U54 (HL112309), and NSF CAREER (1150235) to WAL; as well as an AHA Postdoctoral Fellowship to DRM. DRM thanks CRD and GAK for comments and discussion.

Keywords:

  • Science & Technology
  • Physical Sciences
  • Technology
  • Chemistry, Physical
  • Materials Science, Multidisciplinary
  • Physics, Applied
  • Physics, Condensed Matter
  • Chemistry
  • Materials Science
  • Physics
  • KNOB-HOLE INTERACTIONS
  • CONTRACTILE-FORCE
  • CLOT
  • FIBRIN
  • POLYMERIZATION
  • ELASTICITY
  • ACTIVATION
  • STRESS

Single-platelet nanomechanics measured by high-throughput cytometry

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Journal Title:

Nature Materials

Volume:

Volume 16, Number 2

Publisher:

, Pages 230-235

Type of Work:

Article | Post-print: After Peer Review

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 scaffold1. 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 bleeding2 and thrombotic disorders3. 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.

Copyright information:

© 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.

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