{'fraction_non_alphanumeric': 0.021059782608695652, 'fraction_numerical': 0.0020380434782608695, 'mean_word_length': 5.665158371040724, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Acidic Environment Significantly Alters Aggregation Pathway of Human Islet Amyloid Polypeptide at Negative Lipid Membrane.

The misfolding and aggregation of human islet amyloid polypeptide (hIAPP) at cell membrane has close relationship with the development of type 2 diabetes (T2DM). This aggregation process is susceptible to various physiologically related factors, systematic studies on condition-mediated hIAPP aggregation are therefore essential for a thorough understanding of the pathology of T2DM. In this study, we combined surface-sensitive amide I and amide II spectral signals from the protein backbone, generated simultaneously in a highly sensitive femtosecond broad-band sum frequency generation vibrational spectroscopy system, to examine the effect of environmental pH on the dynamical structural changes of hIAPP at membrane surface in situ and in real time. Such a combination can directly discriminate the formation of β-hairpin-like monomer and oligomer/fibril at the membrane surface. It is evident that, in an acidic milieu, hIAPP slows down its conformational evolution and alters its aggregation pathway, leading to the formation of off-pathway oligomers. When matured hIAPP aggregates are exposed to basic subphase, partial conversion from β-sheet oligomers into ordered β-sheet fibrillar structures is observed. But when exposed to acidic environment, hIAPP fibrils partially converse into more loosely patterned β-sheet oligomeric structures.