Adsorption and Fibrillization of Islet Amyloid Polypeptide at Self-Assembled Monolayers Studied by QCM-D, AFM, and PM-IRRAS
Adsorption and Fibrillization of Islet Amyloid Polypeptide at Self-Assembled Monolayers Studied by QCM-D, AFM, and PM-IRRAS
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DOI：
10.1021/acs.langmuir.7b03626
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发表时间：
2018-03-20
期刊：
影响因子：
3.9
通讯作者：
Keller, Adrian
中科院分区：
文献类型：
--
作者：
Hajiraissi, Roozbeh;Hanke, Marcel;Keller, Adrian
人胰岛淀粉样多肽（hIAPP）的聚集和纤维化在2型糖尿病的发生发展中起重要作用。因此，在分子水平上了解hIAPP与细胞膜等界面的相互作用是迈向新疗法的重要一步。在这里，我们研究了在不同的自组装的烷醇单分子膜（SAMs）的hIAPP的fifluzation石英晶体微天平与耗散监测（QCM-D），原子力显微镜（AFM），和偏振调制红外反射吸收光谱（PM-IRRAS）。我们发现，与CH 3-封端的SAM的疏水相互作用倾向于延迟hIAPP纤维化相比，有吸引力的静电相互作用导致形成的交织原纤维的三维网络的羧酸封端的SAM。在羟基和氨基封端的自组装膜，氟化似乎是由肽和封端基团之间的氢键，这甚至可以克服静电排斥。因此，这些结果提供了基本的见解的分子机制，淀粉样蛋白组装在接口。
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.