Mechanism of fibrin(ogen) forced unfolding.
Mechanism of fibrin(ogen) forced unfolding.
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纤维蛋白（原）强制展开的机制。
DOI：
10.1016/j.str.2011.08.013
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Barsegov,Valeri
中科院分区：
文献类型：
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作者：
Zhmurov,Artem;Brown,AndreEX;Litvinov,RustemI;Dima,RuxandraI;Weisel,JohnW;Barsegov,Valeri
纤维蛋白原，经酶转化为单体纤维蛋白，提供纤维蛋白聚合物的构建块，是血凝块和血栓的支架。尽管纤维蛋白（原）是纤维蛋白的力学和流变特性的基础，对止血至关重要，但对力诱导的纤维蛋白（原）展开知之甚少。通过对纤维蛋白（原）纳米力学特性的实验和理论研究，利用基于原子力显微镜的单分子展开和实验相关时间尺度的模拟，我们确定了纤维蛋白（原）单体和低聚物延伸的机制并绘制了自由能景观。我们发现纤维蛋白（原）的机械解开是由γ链结节的逐步展开和α-螺旋线圈连接器的可逆伸展-收缩相结合的分子转变决定的。这些发现提供了纤维蛋白（原）纳米力学的重要特征，对于理解纤维蛋白粘弹性在纤维和整个凝块水平上的分子起源是必要的。
Fibrinogen, upon enzymatic conversion to monomeric fibrin, provides the building blocks for fibrin polymer, the scaffold of blood clots and thrombi. Little has been known about the force-induced unfolding of fibrin(ogen), even though it is the foundation for the mechanical and rheological properties of fibrin, which are essential for hemostasis. We determined mechanisms and mapped the free energy landscape of the elongation of fibrin(ogen) monomers and oligomers through combined experimental and theoretical studies of the nanomechanical properties of fibrin(ogen), using atomic force microscopy-based single-molecule unfolding and simulations in the experimentally relevant timescale. We have found that mechanical unraveling of fibrin(ogen) is determined by the combined molecular transitions that couple stepwise unfolding of the γ chain nodules and reversible extension-contraction of the α-helical coiled-coil connectors. These findings provide important characteristics of the fibrin(ogen) nanomechanics necessary to understand the molecular origins of fibrin viscoelasticity at the fiber and whole clot levels.