标题： 使用粗粒度正则模态分析的淀粉样纤维机械特性研究 显示英文标题

标题： Mechanical Characterization of Amyloid Fibrils Using Coarse-Grained Normal Mode Analysis

摘要： 最近的实验研究表明，由{\beta }肽聚集形成的淀粉样纤维表现出优异的机械性能，可与其他蛋白质材料如肌动蛋白丝和微管相媲美。 这些优异的机械性能与淀粉样纤维在疾病表达中的功能作用有关。 这表明有必要了解淀粉样纤维如何通过具有结构层次的自聚集实现卓越的机械性能，突出了淀粉样的结构-性能-功能关系，而这种关系仍然不明确。 在本研究中，我们通过粗粒度正则模态分析，研究了人类胰岛淀粉样多肽（hIAPP）的机械性能与其结构层次和结构形状之间的关系。 我们的模拟显示，hIAPP纤维可以通过特定的聚集模式（如{\beta }肽的反平行堆叠）实现优异的弯曲刚度。 此外，我们发现了淀粉样纤维的长度依赖性机械性能。 这种长度依赖性特性已通过考虑剪切效应对淀粉样纤维弯曲影响的Timoshenko梁模型得到阐明。 总之，我们的研究揭示了不仅分子结构（编码纤维的机械性能），而且剪切效应对纤维机械（弯曲）行为的重要性。 显示英文摘要

摘要： Recent experimental studies have shown that amyloid fibril formed by aggregation of {\beta} peptide exhibits excellent mechanical properties comparable to other protein materials such as actin filaments and microtubules. These excellent mechanical properties of amyloid fibrils are related to their functional role in disease expression. This indicates the necessity to understand how an amyloid fibril achieves the remarkable mechanical properties through self-aggregation with structural hierarchy, highlighting the structure-property-function relationship for amyloids, whereas such relationship still remains elusive. In this work, we have studied the mechanical properties of human islet amyloid polypeptide (hIAPP) with respect to its structural hierarchies and structural shapes by coarse-grained normal mode analysis. Our simulation shows that hIAPP fibril can achieve the excellent bending rigidity via specific aggregation pattern such as antiparallel stacking of {\beta} peptides. Moreover, we have found the length-dependent mechanical properties of amyloids. This length-dependent property has been elucidated from Timoshenko beam model that takes into account the shear effect on the bending of amyloids. In summary, our study sheds light on the importance of not only the molecular architecture, which encodes the mechanical properties of the fibril, but also the shear effect on the mechanical (bending) behavior of the fibril.