Atomic force microscopy in biology and biomedicine

In order to gain better understanding of the behavior of complex biological systems, it is sometimes necessary to monitor biological samples in their native state and in their physiological environments. However, until recently, bioscientists have been unable to obtain real-space images of biological and biochemical structures in their physiological aqueous environments with a resolution better than the diffraction limit of conventional optical microscopy, which is approximately 350 nm. The invention of the atomic force microscope by Binnig, Quate and Gerber in 1986 brought new hope in this area. Modifications and improvements to the atomic force microscope in the past two decades have enabled the observation of biological samples from large structures, such as hair and whole cells, down to individual molecules of nucleic acids and proteins with submolecular resolution. This review introduces the basic principles of atomic force microscopy and recent developments in its applications in biological and biochemical research, including those in the fields of virology, bacteriology, cell biology and nucleic acid, protein and peptide studies, as well as electrostatic measurements in biological samples.