Imaging biological samples with the atomic-force microscope

The application of atomic force microscopy (AFM) to biological investigation is attractive for a number of reasons. Foremost among these is the ability of the AFM to image samples, even living cells, under near native conditions and at resolution equal to, or exceeding, that possible by the best light microscopes. Moreover, the ability of the AFM to manipulate samples it images provides a novel and far reaching application of this technology. We have been studying a number of biological samples by AFM. These include conventional and non-conventional nucleic acid structures, ribosomes, neural cells and synapses, cellular organelles (chloroplasts and nuclei), among others. Each of these projects has its own set of associated difficulties and each reveals information about the uses and limits of the AFM in biology. Fig. 1 shows AFM images of various biological samples. In the case of nucleic acids, which have been extensively studied in a number of labs by AFM the problems of signal/noise sample deposition have been overcome in air and organic solvents.