期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1999
卷号：96
期号：7
页码：3688-3693
DOI：10.1073/pnas.96.7.3688
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：We have applied in situ atomic force microscopy to directly observe the aggregation of Alzheimer's {beta}-amyloid peptide (A{beta}) in contact with two model solid surfaces: hydrophilic mica and hydrophobic graphite. The time course of aggregation was followed by continuous imaging of surfaces remaining in contact with 10-500 {micro}M solutions of A{beta} in PBS (pH 7.4). Visualization of fragile nanoscale aggregates of A{beta} was made possible by the application of a tapping mode of imaging, which minimizes the lateral forces between the probe tip and the sample. The size and the shape of A{beta} aggregates, as well as the kinetics of their formation, exhibited pronounced dependence on the physicochemical nature of the surface. On hydrophilic mica, A{beta} formed particulate, pseudomicellar aggregates, which at higher A{beta} concentration had the tendency to form linear assemblies, reminiscent of protofibrillar species described recently in the literature. In contrast, on hydrophobic graphite A{beta} formed uniform, elongated sheets. The dimensions of those sheets were consistent with the dimensions of {beta}-sheets with extended peptide chains perpendicular to the long axis of the aggregate. The sheets of A{beta} were oriented along three directions at 120{degrees} to each other, resembling the crystallographic symmetry of a graphite surface. Such substrate-templated self-assembly may be the distinguishing feature of {beta}-sheets in comparison with -helices. These studies show that in situ atomic force microscopy enables direct assessment of amyloid aggregation in physiological fluids and suggest that A{beta} fibril formation may be driven by interactions at the interface of aqueous solutions and hydrophobic substrates, as occurs in membranes and lipoprotein particles in vivo.
