Fibrin Fiber Stiffness Is Strongly Affected by Fiber Diameter, but Not by Fibrinogen Glycation.
Fibrin Fiber Stiffness Is Strongly Affected by Fiber Diameter, but Not by Fibrinogen Glycation.
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DOI：
10.1016/j.bpj.2016.02.021
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发表时间：
2016-03-29
影响因子：
3.4
通讯作者：
Guthold M
中科院分区：
文献类型：
--
作者：
Li W;Sigley J;Pieters M;Helms CC;Nagaswami C;Weisel JW;Guthold M
血凝块的主要结构成分是纤维蛋白纤维网。我们的目标是确定纤维蛋白原糖化和纤维蛋白纤维直径是否对单纤维蛋白纤维的机械性能有影响。我们使用原子力显微镜/荧光显微镜技术相结合，以确定从血浆中形成的单个纤维蛋白纤维的机械性能。血液样本取自未受控制的糖尿病患者以及年龄、性别和体重指数匹配的健康个体。然后，在采集最终血液样本之前，患者接受治疗以控制血糖水平。糖尿病患者的纤维蛋白原糖化从8.8降至5.0 mol葡萄糖/mol纤维蛋白原，健康个体的平均纤维蛋白原糖化为4.0 mol葡萄糖/mol纤维蛋白原。我们发现，纤维蛋白原糖化对单纤维模量，延展性或应力松弛时间没有显着的系统性影响。然而，我们确实发现纤维模量Y随着纤维直径D的增加而强烈地减小，如。细纤维可以比粗纤维硬100倍。这是不寻常的，因为模量是一个材料常数，不应该取决于均匀材料的样品尺寸（直径）。因此，我们的发现意味着纤维蛋白纤维并不像通常认为的那样具有均匀连接的原纤维的均匀横截面。相反，原纤维连接的密度，ρPb，强烈地随着直径的增加而减小，如。细纤维比粗纤维更致密和/或具有更强连接的原纤维。这意味着由较少的粗纤维组成的凝块比由许多细纤维组成的凝块更容易溶解，这与实验和临床观察结果一致。
The major structural component of a blood clot is a mesh of fibrin fibers. Our goal was to determine whether fibrinogen glycation and fibrin fiber diameter have an effect on the mechanical properties of single fibrin fibers. We used a combined atomic force microscopy/fluorescence microscopy technique to determine the mechanical properties of individual fibrin fibers formed from blood plasma. Blood samples were taken from uncontrolled diabetic patients as well as age-, gender-, and body-mass-index-matched healthy individuals. The patients then underwent treatment to control blood glucose levels before end blood samples were taken. The fibrinogen glycation of the diabetic patients was reduced from 8.8 to 5.0 mol glucose/mol fibrinogen, and the healthy individuals had a mean fibrinogen glycation of 4.0 mol glucose/mol fibrinogen. We found that fibrinogen glycation had no significant systematic effect on single-fiber modulus, extensibility, or stress relaxation times. However, we did find that the fiber modulus, Y, strongly decreases with increasing fiber diameter, D, as . Thin fibers can be 100 times stiffer than thick fibers. This is unusual because the modulus is a material constant and should not depend on the sample dimensions (diameter) for homogeneous materials. Our finding, therefore, implies that fibrin fibers do not have a homogeneous cross section of uniformly connected protofibrils, as is commonly thought. Instead, the density of protofibril connections, ρPb, strongly decreases with increasing diameter, as . Thin fibers are denser and/or have more strongly connected protofibrils than thick fibers. This implies that it is easier to dissolve clots that consist of fewer thick fibers than those that consist of many thin fibers, which is consistent with experimental and clinical observations.