Kinetics of the multistep rupture of fibrin 'A-a' polymerization interactions measured using atomic force microscopy.

Biophysical Journal
Laurel E AverettOleg V Gorkun

Abstract

Fibrin, the structural scaffold of blood clots, spontaneously polymerizes through the formation of 'A-a' knob-hole bonds. When subjected to external force, the dissociation of this bond is accompanied by two to four abrupt changes in molecular dimension observable as rupture events in a force curve. Herein, the configuration, molecular extension, and kinetic parameters of each rupture event are examined. The increases in contour length indicate that the D region of fibrinogen can lengthen by approximately 50% of the length of a fibrin monomer before rupture of the 'A-a' interaction. The dependence of the dissociation rate on applied force was obtained using probability distributions of rupture forces collected at different pull-off velocities. These distributions were fit using a model in which the effects of the shape of the binding potential are used to quantify the kinetic parameters of forced dissociation. We found that the weak initial rupture (i.e., event 1) was not well approximated by these models. The ruptured bonds comprising the strongest ruptures, events 2 and 3, had kinetic parameters similar to those commonly found for the mechanical unfolding of globular proteins. The bonds ruptured in event 4 were well described...Continue Reading

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Citations

Oct 5, 2010·Biophysical Chemistry·Michael R FalvoSusan T Lord
Nov 15, 2011·Structure·Artem ZhmurovValeri Barsegov
May 26, 2010·The Analyst·Laurel E Averett, Mark H Schoenfisch
Jul 17, 2012·Journal of Cell Science·Pere Roca-CusachsMichael P Sheetz
May 26, 2010·Langmuir : the ACS Journal of Surfaces and Colloids·Chad RayBoris B Akhremitchev
Aug 25, 2010·Langmuir : the ACS Journal of Surfaces and Colloids·Laurel E AverettOleg V Gorkun

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