High-resolution imaging of antibodies by tapping-mode atomic force microscopy: attractive and repulsive tip-sample interaction regimes.

A force microscope operated with an amplitude modulation feedback (usually known as tapping-mode atomic force microscope) has two tip-sample interaction regimes, attractive and repulsive. We have studied the performance of those regimes to imaging single antibody molecules. The attractive interaction regime allows determination of the basic morphologies of the antibodies on the support. More importantly, this regime is able to resolve the characteristic Y-shaped domain structure of antibodies and the hinge region between domains. Imaging in the repulsive interaction regime is associated with the irreversible deformation of the molecules. This causes a significant loss in resolution and contrast. Two major physical differences distinguish the repulsive interaction regime from the attractive interaction regime: the existence of tip-sample contact and the strength of the forces involved.