Aggregation and fibrillization of human islet amyloid polypeptide (hIAPP) plays an important role in the development of type 2 diabetes mellitus. Understanding the interaction of hIAPP with interfaces such as cell membranes at a molecular level therefore represents an important step toward new therapies. Here, we investigate the fibrillization of hIAPP at different self-assembled alkanethiol monolayers (SAMs) by quartz crystal microbalance with dissipation monitoring (QCM-D), atomic force microscopy (AFM), and polarization-modulated infrared reflection absorption spectroscopy (PM-IRRAS). We find that hydrophobic interactions with the CH₃-terminated SAM tend to retard hIAPP fibrillization compared to the carboxylic acid-terminated SAM where attractive electrostatic interactions lead to the formation of a three-dimensional network of interwoven fibrils. At the hydroxyl- and amino-terminated SAMs, fibrillization appears to be governed by hydrogen bonding between the peptide and the terminating groups which may even overcome electrostatic repulsion. These results thus provide fundamental insights into the molecular mechanisms governing amyloid assembly at interfaces.

中文翻译：

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QCM-D，AFM和PM-IRRAS研究自组装单层胰岛淀粉样多肽的吸附和原纤维化

人胰岛淀粉样多肽（hIAPP）的聚集和原纤维化在2型糖尿病的发展中起着重要作用。因此，在分子水平上了解hIAPP与界面（例如细胞膜）的相互作用代表了朝着新疗法迈出的重要一步。在这里，我们通过耗散监测（QCM-D），原子力显微镜（AFM）和偏振调制红外反射吸收光谱（PM-IRRAS）通过石英晶体微量天平研究了不同自组装烷硫醇单分子膜（SAMs）上hIAPP的原纤维化）。我们发现与CH _3的疏水相互作用与末端为羧酸的SAM相比，末端为末端的SAM倾向于延迟hIAPP的原纤维化，在末端，有吸引力的静电相互作用导致形成交织原纤维的三维网络。在羟基和氨基末端的SAM处，原纤维化似乎受肽与末端基团之间的氢键控制，甚至可以克服静电排斥。因此，这些结果为控制界面上淀粉样蛋白组装的分子机制提供了基本的见识。