Department of Chemistry, University of Miami, 1301 Memorial Drive, Cox Science Center, Coral Gables, FL 33146, USA.
J R Soc Interface. 2012 Nov 7;9(76):3118-28. doi: 10.1098/rsif.2012.0368. Epub 2012 Jul 11.
Human islet amyloid polypeptide (hIAPP) is the source of the major component of the amyloid deposits found in the islets of Langerhans of around 95 per cent type 2 diabetic patients. The formation of aggregates and mature fibrils is thought to be responsible for the dysfunction and death of the insulin-producing pancreatic β-cells. Investigation on the conformation, orientation and self-assembly of the hIAPP at time zero could be beneficial for our understanding of its stability and aggregation process. To obtain these insights, the hIAPP at time zero was studied at the air-aqueous interface using the Langmuir monolayer technique. The properties of the hIAPP Langmuir monolayer at the air-aqueous interface on a NaCl subphase with pH 2.0, 5.6 and 9.0 were examined by surface pressure- and potential-area isotherms, UV-Vis absorption, fluorescence spectroscopy and Brewster angle microscopy. The conformational and orientational changes of the hIAPP Langmuir monolayer under different surface pressures were characterized by p-polarized infrared-reflection absorption spectroscopy, and the results did not show any prominent changes of conformation or orientation. The predominant secondary structure of the hIAPP at the air-aqueous interface was α-helix conformation, with a parallel orientation to the interface during compression. These results showed that the hIAPP Langmuir monolayer at the air-aqueous interface was stable, and no aggregate or domain of the hIAPP at the air-aqueous interface was observed during the time of experiments.
人胰岛淀粉样多肽(hIAPP)是 95%的 2 型糖尿病患者胰岛中发现的淀粉样沉积物的主要成分来源。聚集物和成熟原纤维的形成被认为是导致胰岛素产生的胰腺β细胞功能障碍和死亡的原因。对 hIAPP 在零时的构象、取向和自组装进行研究可能有助于我们理解其稳定性和聚集过程。为了获得这些见解,使用 Langmuir 单层技术在气-水界面研究了零时的 hIAPP。通过表面压力和电位-面积等温线、紫外-可见吸收、荧光光谱和布鲁斯特角显微镜研究了在 pH 2.0、5.6 和 9.0 的 NaCl 亚相上气-水界面上 hIAPP 的 Langmuir 单层的性质。通过 p 偏振红外反射吸收光谱研究了 hIAPP Langmuir 单层在不同表面压力下的构象和取向变化,结果没有显示出任何明显的构象或取向变化。hIAPP 在气-水界面上的主要二级结构是α-螺旋构象,在压缩过程中与界面平行取向。这些结果表明,气-水界面上的 hIAPP Langmuir 单层是稳定的,在实验期间没有观察到气-水界面上 hIAPP 的聚集或域。