Intermolecular forces between acetylcholine and acetylcholinesterases studied with atomic force microscopy

With the aid of atomic force microscopy, the intermolecular forces between acetylcholinesterases (AChE) and its natural substrate acetylcholine (ACh) have been studied. Through force spectrum measurement based on imaging of AChE molecules it was found that the attraction force between individual molecule pairs of ACh and AChE was (10 ± 1) pN just before the quaternary ammonium head of ACh got into contact with the negative end of AChE and the decaying distance of attraction was (4± 1) nm from the surface of AChE. The adhesion force between individual ACh and AChE molecule pairs was (25± 2) pN, which had a decaying feature of fast-slow-fast (FSF). The attraction forces between AChE and choline (Ch), the quaternary ammonium moiety and hydrolysate of ACh molecule, were similar to those between AChE and ACh. The adhesion forces between AChE and Ch were (20 ± 2) pN, a little weaker than that between ACh and AChE. These results indicated that AChE had a steering role for the diffusion of ACh toward it and had resistance against the leave of Ch along the original way along which it came into contact with AChE as the quaternary moiety of ACh. Project supported by the National Natural Science Foundation of China (Grant Nos. 19634010, 39780041) and Important Subject of the Chinese Academy of Sciences.