[PDF][PDF] α− α Cross-links increase fibrin fiber elasticity and stiffness

CC Helms, RAS Ariëns, SU De Willige, KF Standeven… - Biophysical journal, 2012 - cell.com
CC Helms, RAS Ariëns, SU De Willige, KF Standeven, M Guthold
Biophysical journal, 2012cell.com
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 …
Abstract
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 αα 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 αα 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.
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