Nassar Roy, Wong Eric, Bui Jennifer M, Yip Calvin K, Li Hongbin, Gsponer Jörg, Lamour Guillaume
Michael Smith Laboratories , The University of British Colombia , Vancouver , BC Canada V6T 1Z4.
Department of Biochemistry & Molecular Biology , The University of British Colombia , Vancouver , BC Canada V6T 1Z3.
J Phys Chem Lett. 2018 Sep 6;9(17):4901-4909. doi: 10.1021/acs.jpclett.8b02027. Epub 2018 Aug 15.
Mapping the nanomechanical properties of amyloids can provide valuable insights into structure and assembly mechanisms of protein aggregates that underlie the development of various human diseases. Although it is well-known that amyloids exhibit an intrinsic stiffness comparable to that of silk (1-10 GPa), a detailed understanding of the directional dependence (anisotropy) of the stiffness of amyloids and how it relates to structural features in these protein aggregates is missing. Here we used steered molecular dynamics (SMD) simulations and amplitude modulation-frequency modulation (AM-FM) atomic force microscopy to measure the directional variation in stiffness of GNNQQNY amyloid crystals. We reveal that individual crystals display significant mechanical anisotropy and relate this anisotropy to subtle but mechanically important differences in interactions between interfaces that define the crystal architecture. Our results provide detailed insights into the structure-mechanics relationship of amyloid that may help in designing amyloid-based nanomaterials with tailored mechanical properties.
绘制淀粉样蛋白的纳米力学特性图，可以为各种人类疾病发展所依赖的蛋白质聚集体的结构和组装机制提供有价值的见解。尽管众所周知，淀粉样蛋白表现出与丝绸相当的固有刚度（1-10吉帕斯卡），但对淀粉样蛋白刚度的方向依赖性（各向异性）及其与这些蛋白质聚集体结构特征的关系仍缺乏详细了解。在此，我们使用引导分子动力学（SMD）模拟和调幅-调频（AM-FM）原子力显微镜来测量GNNQQNY淀粉样晶体刚度的方向变化。我们发现，单个晶体表现出显著的力学各向异性，并将这种各向异性与定义晶体结构的界面间相互作用中细微但对力学至关重要的差异联系起来。我们的结果为淀粉样蛋白的结构-力学关系提供了详细见解，这可能有助于设计具有定制力学性能的基于淀粉样蛋白的纳米材料。
