Molecular basis of fibrin clot elasticity
Molecular basis of fibrin clot elasticity
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DOI：
10.1016/j.str.2007.12.019
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发表时间：
2008-03-01
期刊：
影响因子：
5.7
通讯作者：
Schulten, Klaus
中科院分区：
文献类型：
--
作者：
Lim, Bernard B. C.;Lee, Eric H.;Schulten, Klaus
血凝块必须坚硬才能止血，同时必须具有弹性才能缓冲血液的剪切力。打破这种平衡会导致血栓破裂和危及生命的血栓栓塞。纤维蛋白是血凝块的主要成分，由凝血酶激活的纤维蛋白原分子形成。尽管众所周知纤维蛋白具有相当大的弹性，但这种弹性的分子基础尚不清楚。在这里，我们使用原子力显微镜（AFM）和引导分子动力学（SMD）来探测单个纤维蛋白原分子和纤维蛋白原纤维的机械特性，表明它们的卷曲螺旋α螺旋的机械展开的特征是系统的力延伸曲线中独特的中间力平台。我们将这种平台力与纤维蛋白原卷曲α螺旋及其中心结构域的逐步展开联系起来。 AFM 数据显示，不同的 pH 值和钙离子浓度会改变纤维蛋白原的机械弹性。这项研究为纤维蛋白原卷曲的α螺旋带来纤维蛋白弹性提供了直接证据。
Blood clots must be stiff to stop hemorrhage yet elastic to buffer blood's shear forces. Upsetting this balance results in clot rupture and life-threatening thromboembolism. Fibrin, the main component of a blood clot, is formed from molecules of fibrinogen activated by thrombin. Although it is well known that fibrin possesses considerable elasticity, the molecular basis of this elasticity is unknown. Here, we use atomic force microscopy (AFM) and steered molecular dynamics (SMD) to probe the mechanical properties of single fibrinogen molecules and fibrin protofibrils, showing that the mechanical unfolding of their coiled-coil alpha helices is characterized by a distinctive intermediate force plateau in the systems' force-extension curve. We relate this plateau force to a stepwise unfolding of fibrinogen's coiled alpha helices and of its central domain. AFM data show that varying pH and calcium ion concentrations alters the mechanical resilience of fibrinogen. This study provides direct evidence for the coiled alpha helices of fibrinogen to bring about fibrin elasticity.