Web Release Date: March 20,
Complexity of "A-a" Knob-Hole Fibrin Interaction Revealed by Atomic Force Spectroscopy
and
Department of Physics and Astronomy, Department of Chemistry, and Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, North Carolina 27599, and Department of Chemistry, Duke University, Durham, North Carolina 27708
Received October 19, 2007
In Final Form: December 18, 2007
Abstract:
During blood vessel injury, fibrinogen is converted to fibrin, a polymer that serves as the structural scaffold of a blood clot. The primary function of fibrin is to withstand the large shear forces in blood and provide mechanical stability to the clot, protecting the wound. Understanding the biophysical forces involved in maintaining fibrin structure is of great interest to the biomedical community. Previous reports have identified the "A-a" knob-hole interaction as the dominant force responsible for fibrin's structural integrity. Herein, biochemical force spectroscopy is used to study knob-hole interactions between fibrin fragments and variant fibrinogen molecules to identify the forces occurring between individual fibrin molecules. The rupture of the "A-a" knob-hole interaction results in a characteristic profile previously unreported in fibrin force spectroscopy with two distinct populations of specific forces: 110 ± 34 and 224 ± 31 pN. In the absence of a functional "A" knob or hole "a", these forces cease to exist. We propose that the characteristic pattern represents the deformation of the D region of fibrinogen prior to the rupture of the "A-a" knob-hole bond.
Download the full text: PDF | HTML
