Chen Hao, Sun Dan, Tian Yin, Fan Haiming, Liu Yonggang, Morozova-Roche Ludmilla A, Zhang Ce
School of Chemical Engineering, Northwest University, Xi'an 710069, China.
State Key Laboratory of Cultivation Base for Photoelectric Technology and Functional Materials, Institute of Photonics and Photon-Technology, Northwest University, Xi'an 710069, China.
ACS Omega. 2020 Feb 6;5(6):2856-2864. doi: 10.1021/acsomega.9b03671. eCollection 2020 Feb 18.
The transition of amyloidogenic species into ordered structures (i.e., prefibrillar oligomers, protofibrils, mature fibrils, and amyloidogenic aggregates) is closely associated with many neurodegenerative disease pathologies. It is increasingly appreciated that the liquid-solid interface contributes to peptide aggregation under physiological conditions. However, much remains to be explored on the molecular mechanism of surface-directed amyloid formation. We herein demonstrate that physical environmental conditions (i.e., negatively charged surface) affect amyloid formation. Nontoxic amyloid aggregates quickly develop into intertwisting fibrils on a negatively charged mica surface. These fibrillar structures show significant cytotoxicity on both neuroblastoma cell-lines (SH-SY5Y) and primary neural stem cells. Our results suggest an alternative amyloid development pathway, following which Aβ peptides form large amyloidogenic aggregates upon stimulation, and later transit into neurotoxic fibrillar structures while being trapped and aligned by a negatively charged surface. Conceivably, the interplay between chemical and physical environmental conditions plays important roles in the development of neurodegenerative diseases.
淀粉样蛋白生成物种向有序结构（即原纤维前体寡聚物、原纤维、成熟纤维和淀粉样蛋白生成聚集体）的转变与许多神经退行性疾病病理密切相关。人们越来越认识到，液固界面在生理条件下有助于肽聚集。然而，关于表面定向淀粉样蛋白形成的分子机制仍有许多有待探索之处。我们在此证明，物理环境条件（即带负电荷的表面）会影响淀粉样蛋白的形成。无毒的淀粉样蛋白聚集体在带负电荷的云母表面迅速发展成缠绕的纤维。这些纤维状结构对神经母细胞瘤细胞系（SH-SY5Y）和原代神经干细胞均表现出显著的细胞毒性。我们的结果提示了一种淀粉样蛋白的替代发展途径，即Aβ肽在受到刺激后形成大型淀粉样蛋白生成聚集体，随后在被带负电荷的表面捕获并排列时转变为神经毒性纤维状结构。可以想象，化学和物理环境条件之间的相互作用在神经退行性疾病的发展中起着重要作用。
