title: Fibrin Fiber Stiffness Is Strongly Affected by Fiber Diameter, but Not by Fibrinogen Glycation.
abstract: The major structural component of a blood clot is a mesh of fibrin fibers. Our goal was to determine whether fibrinogen glycation and fibrin fiber diameter have an effect on the mechanical properties of single fibrin fibers. We used a combined atomic force microscopy/fluorescence microscopy technique to determine the mechanical properties of individual fibrin fibers formed from blood plasma. Blood samples were taken from uncontrolled diabetic patients as well as age-, gender-, and body-mass-index-matched healthy individuals. The patients then underwent treatment to control blood glucose levels before end blood samples were taken. The fibrinogen glycation of the diabetic patients was reduced from 8.8 to 5.0 mol glucose/mol fibrinogen, and the healthy individuals had a mean fibrinogen glycation of 4.0 mol glucose/mol fibrinogen. We found that fibrinogen glycation had no significant systematic effect on single-fiber modulus, extensibility, or stress relaxation times. However, we did find that the fiber modulus, Y, strongly decreases with increasing fiber diameter, D, as Y∝D(-1.6). Thin fibers can be 100 times stiffer than thick fibers. This is unusual because the modulus is a material constant and should not depend on the sample dimensions (diameter) for homogeneous materials. Our finding, therefore, implies that fibrin fibers do not have a homogeneous cross section of uniformly connected protofibrils, as is commonly thought. Instead, the density of protofibril connections, ρPb, strongly decreases with increasing diameter, as ρPb∝D(-1.6). Thin fibers are denser and/or have more strongly connected protofibrils than thick fibers. This implies that it is easier to dissolve clots that consist of fewer thick fibers than those that consist of many thin fibers, which is consistent with experimental and clinical observations.
authors.affiliation: Department of Physics, Wake Forest University, Winston-Salem, North Carolina.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Physics, Wake Forest University, Winston-Salem, North Carolina.
authors.forename: Justin
authors.initials: J
authors.lastname: Sigley
authors.affiliation: Centre of Excellence for Nutrition, North-West University, Potchefstroom, South Africa.
authors.forename: Marlien
authors.initials: M
authors.lastname: Pieters
authors.affiliation: Department of Physics, University of Richmond, Richmond, Virginia.
authors.forename: Christine Carlisle
authors.initials: CC
authors.lastname: Helms
authors.affiliation: Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Chandrasekaran
authors.initials: C
authors.lastname: Nagaswami
authors.affiliation: Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.
authors.forename: John W
authors.initials: JW
authors.lastname: Weisel
authors.affiliation: Department of Physics, Wake Forest University, Winston-Salem, North Carolina. Electronic address: gutholdm@wfu.edu.
authors.forename: Martin
authors.initials: M
authors.lastname: Guthold
mesh_terms: D000328:Adult; D000368:Aged; D001696:Biomechanical Phenomena; D018360:Crystallography, X-Ray; D055119:Elastic Modulus; D005260:Female; D005337:Fibrin / Q000737:chemistry*; D005340:Fibrinogen / Q000737:chemistry*; D006031:Glycosylation; D006801:Humans; D008875:Middle Aged; D055682:Viscoelastic Substances
chemical_list: D055682:Viscoelastic Substances; D005337:Fibrin; D005340:Fibrinogen