α-α Cross-links increase fibrin fiber elasticity and stiffness.
Fibrin fibers, which are ~100 nm in diameter, are the major structural component of a blood clot. The mechanical properties of single fibrin fibers determine the behavior of a blood clot and, thus, have a critical influence on heart attacks, strokes, and embolisms. Cross-linking is thought to fortify blood clots; though, the role of α-α cross-links in fibrin fiber assembly and their effect on the mechanical properties of single fibrin fibers are poorly understood. To address this knowledge gap, we used a combined fluorescence and atomic force microscope technique to determine the stiffness (modulus), extensibility, and elasticity of individual, uncross-linked, exclusively α-α cross-linked (γQ398N/Q399N/K406R fibrinogen variant), and completely cross-linked fibrin fibers. Exclusive α-α cross-linking results in 2.5× stiffer and 1.5× more elastic fibers, whereas full cross-linking results in 3.75× stiffer, 1.2× more elastic, but 1.2× less extensible fibers, as compared to uncross-linked fibers. On the basis of these results and data from the literature, we propose a model in which the α-C region plays a significant role in inter- and intralinking of fibrin molecules and protofibrils, endowing fibrin fibers with increased stiffness and elasticity.
Department of Physics, Wake Forest University, Winston-Salem, North Carolina, USA.
Christine C
CC
Helms
Robert A S
RA
Ariëns
S
S
Uitte de Willige
Kristina F
KF
Standeven
Martin
M
Guthold
D001665:Binding Sites; D003198:Computer Simulation; D003432:Cross-Linking Reagents / Q000737:chemistry*; D055119:Elastic Modulus; D005337:Fibrin / Q000737:chemistry*; D008956:Models, Chemical; D008958:Models, Molecular; D011485:Protein Binding; D013314:Stress, Mechanical; D013718:Tensile Strength
D003432:Cross-Linking Reagents; D005337:Fibrin