Technical and Macromolecular Chemistry , Paderborn University , Warburger Str. 100 , 33098 Paderborn , Germany.
Langmuir. 2018 Mar 20;34(11):3517-3524. doi: 10.1021/acs.langmuir.7b03626. Epub 2018 Mar 6.
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 CH-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.
人胰岛淀粉样多肽（hIAPP）的聚集和纤维化在 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 与细胞膜等界面的相互作用是新疗法的重要步骤。在这里，我们通过石英晶体微天平耗散监测（QCM-D）、原子力显微镜（AFM）和偏振调制红外反射吸收光谱（PM-IRRAS）研究了 hIAPP 在不同自组装烷硫醇单层（SAM）上的纤维化。我们发现，与羧酸端 SAM 相比，与 CH 端 SAM 的疏水相互作用往往会延缓 hIAPP 的纤维化，因为静电吸引相互作用会导致交织纤维的三维网络形成。在羟基和氨基端 SAM 上，纤维化似乎受肽和末端基团之间氢键的控制，甚至可能克服静电排斥。这些结果为界面上淀粉样蛋白组装的分子机制提供了基本的见解。
