Experiment-based multi-scale modeling of the tensile and compressive deformations of fibrin

纤维蛋白拉伸和压缩变形的多尺度实验模拟 普拉尚特·K·普罗希特和约翰·W·韦塞尔 宾夕法尼亚大学，费城，宾夕法尼亚州19104。 文摘：该方案的研究目标是测量、建模和预测拉伸和 纤维蛋白凝块在分子和连续尺度上的压缩响应。这一点很重要，因为 没有全面的模型将分子力学与凝块的宏观变形联系起来 血栓，即使它们在正常功能过程中经历了所有尺度的变形/改变 止血和血栓形成的病理情况。我们已经证明，大量的纤维蛋白凝块可以 由于纤维蛋白的机械展开，拉伸到原来长度的三到四倍 纳米级的单体。在压缩中，我们已经证明了凝块的变形是类似的。 到泡沫，并通过压缩锋面的运动进行，在压缩锋面后面，网络因 到纤维的弯曲和纤维间接触的产生。这些功能在我们的模型中捕捉到，可以 定量地描述和预测分子和纤维水平的力学如何对 凝块的宏观反应。我们的模型允许我们通过以下方式调整凝块的宏观力学行为 改变网络的分子组成单元和结构参数。这一想法将被提交给 当我们(A)通过改变网络结构来调制凝块的平衡拉伸响应时进行测试 参数，以及(B)研究低聚物的交联度如何影响拉伸响应的依赖性 在应变率上。我们还可以改变纤维蛋白的纳米级结构，并使用我们的模型来预测 对肉眼血块的影响。我们的目标是纤维蛋白的C区域，已知该区域根据不同的 在物种上，并已被证明在控制单一的拉伸硬度和延伸率方面起作用。 纤维蛋白纤维和纤维蛋白凝块。对于压缩，我们将显示贫血小板血浆的变形 血栓、富含血小板的血浆凝块、全血凝块和血栓也呈泡沫状，然后预测和测量 它们对局部载荷的反应。这种局部负荷在临床情况下可能会遇到，例如 导管或气泡与血栓的相互作用。我们还将调查C区对 凝块的压缩反应。我们的模型是基于连续介质力学原理来研究的 聚合物材料和泡沫，以及描述单个受迫展开的统计力学模型 蛋白质分子。建议的实验涵盖了宏观单轴拉伸试验的全部范围， 原子力显微镜实验包括齐聚物的拉伸和凝块的压痕，流变学 测量压缩、电子显微镜和荧光显微镜中的存储和损耗模数 以可视化纤维蛋白凝块的结构。我们的模型和实验将有助于回答临床上重要的问题 问题，例如为什么凝块结构/机械性能和 心血管疾病，还有助于设计具有独特机械性能的生物材料 纤维蛋白的纳米级结构。

Experiment-based multi-scale modeling of the tensile and compressive deformations of fibrin Prashant K. Purohit and John W. Weisel University of Pennsylvania, Philadelphia, PA 19104. Abstract: The research objective of this proposal is to measure, model and predict the tensile and compressive response of fibrin clots at the molecular and continuum scales. This is important because there are no comprehensive models that link the molecular mechanics to the macroscopic deformation of clots and thrombi, even though they experience deformation/alteration at all scales during their normal function in hemostasis and in pathological situations of thrombosis. We have shown that macroscale fibrin clots can be stretched to three or four times their original length in uniaxial tension due to mechanical unfolding of fibrin monomers at the nanometer scale. In compression, we have shown that the deformation of a clot is analogous to that of a foam and proceeds by the motion of a compression front, behind which the network densifies due to buckling of fibers and creation of inter-fiber contacts. These features are captured in our models that can quantitatively describe and predict how molecular and fiber level mechanics has implications for the macroscopic response of clots. Our models allow us to tune the macroscale mechanical behavior of clots by altering the molecular building blocks and the structural parameters of the network. This idea will be put to the test when we (a) modulate the equilibrium tensile response of clots by altering the network structural parameters, and (b) investigate how cross-linking of oligomers affects the dependence of the tensile response on the strain rate. We can also alter the nanoscale structure of fibrin and use our model to predict the consequences for macroscopic clots. Our target is the  C region of fibrin, which is known to vary depending on the species and has been shown to play a part in controlling the tensile stiffness and extensibility of single fibrin fibers as well fibrin clots. For compression, we will show that the deformation of platelet-poor plasma clots, platelet-rich plasma clots, whole blood clots and thrombi is also foam-like, and then predict and measure their response to localized loads. Such localized loads could be encountered in clinical situations, such as the interaction of catheters or bubbles with thrombi. We will also investigate the effect of the  C region on the compression response of clots. Our models are based on continuum mechanical principles for the study of polymeric materials and foams, as well as statistical mechanics models describing forced unfolding of single protein molecules. The proposed experiments cover the whole gamut of macroscopic uniaxial tension tests, atomic force microscopy experiments including stretching of oligomers and indentation of clots, rheometry to measure the storage and loss moduli in compression, electron microscopy as well as fluorescence microscopy to visualize the structure of fibrin clots. Our models and experiments will help answer clinically important questions, such as why is there a strong correlation between clot structure/mechanical properties and cardiovascular disease, and also help design biomaterials with unique mechanical properties by altering the structure of fibrin at the nanoscale.