Force clamp approach for characterization of nano-assembly in amyloid beta 42 dimer.

Amyloid β (Aβ) oligomers are formed at the early stages of the amyloidogenesis process and exhibit neurotoxicity. Development of oligomer specific therapeutics requires a detailed understanding of oligomerization processes. Amyloid oligomers exist transiently and single-molecule approaches are capable of characterizing such species. In this paper, we describe the application of an AFM based force clamp approach for probing of Aβ42 dimers. Aβ42 monomers were tethered to the AFM tip and surface and the dimers are formed during the approaching the tip to the surface. AFM force clamp experiments were performed at different force clamps. They revealed two types of transient states for dissociating Aβ42 dimers. The analysis showed that these states have distinct lifetimes of 188 ± 52 milliseconds (type 1, short lived) and 317 ± 67 milliseconds (type 2, long lived). Type 1 state prevails over type 2 state as the value of the applied force increases. The rupture lengths analysis led to the models of the dimer dissociation pathways that are proposed.