The elasticity of an individual fibrin fiber in a clot

doi:10.1073/pnas.0504120102

The elasticity of an individual fibrin fiber in a clot

^*Department of Cell and Developmental Biology and ^‡Institute for Environmental Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104; and ^†Department of Cardiology, Pitié-Salpêtrière Hospital, 95013 Paris, France

Communicated by Laszlo Lorand, Northwestern University Feinberg School of Medicine, Chicago, IL, May 18, 2005 (received for review August 25, 2004)

Abstract

A blood clot needs to have the right degree of stiffness and plasticity to stem the flow of blood and yet be digestable by lytic enzymes so as not to form a thrombus, causing heart attacks, strokes, or pulmonary emboli, but the origin of these mechanical properties is unknown. Clots are made up of a three-dimensional network of fibrin fibers stabilized through ligation with a transglutaminase, factor XIIIa. We developed methods to measure the elastic moduli of individual fibrin fibers in fibrin clots with or without ligation, using optical tweezers for trapping beads attached to the fibers that functioned as handles to flex or stretch a fiber. Here, we report direct measurements of the microscopic mechanical properties of such a polymer. Fibers were much stiffer for stretching than for flexion, as expected from their diameter and length. Elastic moduli for individual fibers in plasma clots were 1.7 ± 1.3 and 14.5 ± 3.5 MPa for unligated and ligated fibers, respectively. Similar values were obtained by other independent methods, including analysis of measurements of fluctuations in bead force as a result of Brownian motion. These results provide a basis for understanding the origin of clot elasticity.

Footnotes

↵ § To whom correspondence should be addressed at: Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Room 1054 BRBII/III, 421 Curie Boulevard, Philadelphia, PA 19104-6058. E-mail: weisel{at}mail.med.upenn.edu.
Author contributions: J.-P.C., H.S., and J.W.W. designed research; J.-P.C. and S.L. performed research; J.-P.C., H.S., R.E.L., and J.W.W. contributed new reagents/analytic tools; J.-P.C., H.S., R.E.L., S.L., and J.W.W. analyzed data; and J.-P.C., H.S., and J.W.W. wrote the paper.
Abbreviation: DDITS, 1,3-dimethyl-4,5-diphenyl-2[2(oxopropyl)thio]imidazolium trifluoromethyl-sulfonate.
↵ ¶ Scientists studying fibrin have called this process “crosslinking,” but to avoid confusion among polymer chemists and materials scientists, we have used the more proper term, “ligation.”