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The aggregation of amyloid peptides into ordered fibrils is closely associated with many neurodegenerative diseases. The surfaces of cell membranes and biomolecules are believed to play important roles in modulation of peptide aggregation under physiological conditions. Experimental studies of fibrillogenesis at the molecular level in vivo, however, are inherently challenging, and the molecular mechanisms of how surface affects the structure and ordering of amyloid fibrils still remain elusive. Herein we have investigated the aggregation behavior of insulin peptides within water films adsorbed on the mica surface. AFM measurements revealed that the structure and orientation of fibrils were significantly affected by the mica lattice and the peptide concentration. At low peptide concentration (∼0.05 mg mL -1), there appeared a single layer of short and well oriented fibrils with a mean height of 1.6 nm. With an increase of concentration to a range of 0.2-2.0 mg mL-1, a different type of fibrils with a mean height of 3.8 nm was present. Interestingly, when the concentration was above 2.0 mg mL-1, the thicker fibrils exhibited two-dimensional liquid-crystal-like ordering probably caused by the combination of entropic and electrostatic forces. These results could help us gain better insight into the effects of the substrate on amyloid fibrillation.

The process of glucagon peptide aggregation was studied with high resolution atomic force microscopy (AFM). The statistical analysis of ex situ AFM images in combination with in situ AFM observation suggests that it is more likely that (proto)fibrils are formed via direct longitudinal growth of oligomers, instead of the lateral association of two or more filaments.