A Modular Fibrinogen Model that Captures the Stress-Strain Behavior of?Fibrin Fibers

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• 作者：Rodney?D. Averett ; Bryant Menn ; Eric?H. Lee ; Christine?C. Helms ; Thomas Barker ; Martin Guthold
• 刊名：Biophysical Journal
• 出版年：2012
• 出版时间：3 October, 2012
• 年：2012
• 卷：103
• 期：7
• 页码：1537-1544
• 全文大小：628 K

文摘

We tested what to our knowledge is a new computational model for fibrin fiber mechanical behavior. The model is composed of three distinct elements: the folded fibrinogen core as seen in the crystal structure, the unstructured ¦Á-C connector, and the partially folded ¦Á-C domain. Previous studies have highlighted the importance of all three regions and how they may contribute to fibrin fiber stress-strain behavior. Yet no molecular model has been computationally tested that takes into account the individual contributions of all these regions. Constant velocity, steered molecular dynamics studies at 0.025??/ps were conducted on the folded fibrinogen core and the ¦Á-C domain to determine their force-displacement behavior. A wormlike chain model with a persistence length of 0.8?nm (Kuhn length?= 1.6?nm) was used to model the mechanical behavior of the unfolded ¦Á-C connector. The three components were combined to calculate the total stress-strain response, which was then compared to experimental data. The results show that the three-component model successfully captures the experimentally determined stress-strain behavior of fibrin fibers. The model evinces the key contribution of the ¦Á-C domains to fibrin fiber stress-strain behavior. However, conversion of the ¦Á-helical coiled coils to ¦Â-strands, and partial unfolding of the protein, may also contribute.