Electrostatically balanced subnanometer imaging of biological specimens byatomic force microscope

To achieve high-resolution topographs of native biological macromolecules i n aqueous solution with the atomic force microscope (AFM) interactions betw een AFM tip and sample need to be considered. Short-range forces produce th e submolecular information of high-resolution topographs. In contrast, no s ignificant high-resolution information is provided by the long-range electr ostatic double-layer force. However, this force can be adjusted by pH and e lectrolytes to distribute the force applied to the AFM tip over a large sam ple area. As demonstrated on fragile biological samples, adjustment of the electrolyte solution results in a local reduction of both vertical and late ral forces between the AFM tip and proteinous substructures. Under such ele ctrostatically balanced conditions. the deformation of the native protein i s minimized and the sample surface can be reproducibly contoured at a later al resolution of 0.6 nm.