生物分子
纳米技术
原子力显微镜
纳米尺度
分子
纳米材料
淀粉样纤维
表征(材料科学)
化学
高分子
材料科学
生物物理学
淀粉样β
生物
有机化学
病理
疾病
医学
生物化学
作者
Francesco Simone Ruggeri,Tomas Šneideris,Michele Vendruscolo,Tuomas P. J. Knowles
标识
DOI:10.1016/j.abb.2019.02.001
摘要
The development of atomic force microscopy (AFM) has opened up a wide range of novel opportunities in nanoscience and new modalities of observation in complex biological systems. AFM imaging has been widely employed to resolve the complex and heterogeneous conformational states involved in protein aggregation at the single molecule scale and shed light onto the molecular basis of a variety of human pathologies, including neurodegenerative disorders. The study of individual macromolecules at nanoscale, however, remains challenging, especially when fully quantitative information is required. In this review, we first discuss the principles of AFM with a special emphasis on the fundamental factors defining its sensitivity and accuracy. We then review the fundamental parameters and approaches to work at the limit of AFM resolution in order to perform single molecule statistical analysis of biomolecules and nanoscale protein aggregates. This single molecule statistical approach has proved to be powerful to unravel the molecular and hierarchical assembly of the misfolded species present transiently during protein aggregation, to visualise their dynamics at the nanoscale, as well to study the structural properties of amyloid-inspired functional nanomaterials.
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