At present, changes in the structure of proteins occurring upon adsorption at liquid/solid interfaces are not well understood. The prevailing model assumes that a protein, which is globular in solution, must first displace surface bound water molecules. Then, after adsorption of the protein at the surface, the molecule unfolds to maximize interactions with the surface. It is noted, however, that some enzymes maintain a significant amount of their activity once adsorbed. This observation is the basis for many biomedical assays and implies that native protein structure is at least partially maintained.

The atomic force microscope (AFM) is well suited for the study of biomolecules at interfaces, providing single molecule resolution. Progress on molecular structure analysis of proteins using AFM, however, has been hampered by the fact that the tip radius is as large as, or larger than the proteins themselves, thereby causing a large lateral convolution effect.