The Gentle Touch: Probing Cells and Molecules by Atomic Force Microscopy

Dr. Jan H. Hoh
Department of Physiology
Johns Hopkins School of Medicine

The atomic force microscope (AFM) is emerging as a powerful tool for understanding the structure, chemistry and physical properties of a wide variety of biological materials ranging from molecules to living cells.  The AFM is based on a sharp probe mounted on a small microfabricated spring, where interactions of the probe with a sample are measured through deflections of the spring.  An optical detection system allows movements of the spring smaller than 0.01 nanometers to be measured.  By moving the probe in a raster pattern across molecules such as proteins and DNA bound to a flat surface, the shapes of these molecules can be determined with a resolution on the order of 1 nanometer.  The spring also allows the AFM to be used as a force sensor.  For example, attaching one protein to the probe and another to a support, interaction forces between the two molecules can be measured with picoNewton sensitivity.  When imaging living cells with the AFM the force applied by the spring causes soft parts of the cells to deform more than stiff parts, thus providing a “picture” of the mechanical properties of the cells.  These and other applications of AFM to biological systems will be presented; what emerges from this new technology is a unique view on the building blocks that make up living systems.