Structure, Flexibility and Intramolecular Forces Observed on Individual Proteins Using Afm

Abstract Atomic force microscopy (AFM) allows the surfaces of native biological macromolecules to be imaged in aqueous solution with submolecular resolution. Short range forces govern the interactions between the AFM tip and the sample and produce the submolecular information of high resolution topographs. In contrast, the long range electrostatic double-layer (EDL) force can be adjusted by pH and electrolytes to distribute the force applied to the AFM tip over a large sample area [1]. As demonstrated on fragile biological samples, adjustment of the electrolyte solution results in a local reduction of both vertical and lateral forces between the AFM tip and proteineous substructures. Consequently, the deformation of the native protein is minimized and polypeptide loops of individual proteins were imaged in aqueous solution with a lateral resolution < 5 Åand a vertical resolution < 1 Å (Fig. 1).