Atomic force spectroscopy(AFM)based singlemolecule force spectroscopy(SMFS) can serve as an important tool for studying intramolecular and intermolecular interactions at single-molecule level.On the basis of our recent work

this feature article is aimed to introduce how to combine the delicate SMFS with elegant self-assembly for direct measurements of different intermolecular intera ctions

including π-π interaction

multivalency and intercalation interaction.To realize the force measurement of singlemolecule rupture

one of the interacting components needs to be covalently attached to AFM tip through a flexible polyethylene glycol(PEG) spacer

and the other component to the substrate surface.By the movement of piezo tube

the force-extension curve can be obtained.The introduction of PEG as a spacer provides a means for differentiating the force signal based on the extension length as well as for avoiding the disturbance of the non-specific interaction between the AFM tip and the substrate.In addition

with dynamic force spectroscopy

details about the kinetic of the unbinding and information concerning the length scale of the interaction can be extracted.Therefore

SMFS can investigate not only the intermolecular interactions directly

but also physical insight of the interactions

thus guiding molecular selfassem bly.