With the development of nanotechnology, understanding of intermolecular interactions on a single molecule level by atomic force spectroscopy (AFM) has played an important role in molecular biology and biomedical science. In recent years, some research suggested that the presence of metal cations is an important regulator in the processes of misfolding and aggregation of the amyloid beta-protein (A beta), which may be an important etiological factor of Alzheimer's disease. However, the knowledge on the principle of interactions between A beta and metal cations at the single molecule level is still poor understood. In this paper, the amyloid beta-protein (A beta) was fabricated on substrate of mixed thiol-modified gold nanoparticles using self-assembled monolayer method and the adhesion force in the longitudinal direction between metal cations and A beta 42 were investigated by AFM. The role of metal ions on A beta aggregation is discussed from the perspective of single molecular force. The force results showed that the specific adhesion force F-i and the nonspecific force F-0 between a single A beta-A beta pair in control experiment were calculated as 42 +/- 3 and 80 pN, respectively. However, Fi between a single A beta-A beta pair in the presence of Cu2+, Zn2+, Ca2+ and Al3+ increased dramatically to 84 +/- 6, 89 +/- 3, 73 +/- 5, 95 +/- 5 pN successively, which indicated that unbinding between A beta proteins is accelerated in the presence of metal cations. What is more, the imaging results showed that substoichiometric copper cations accelerate the formation of fibrils within 3 days. The combined atomic force spectroscopy and imaging analysis indicate that metal cations play a role in promoting the aggregating behavior of A beta 42.